Seryl-lysyl-based peptide and peptidomimetic inhibitors of N-myristoyl transferase as anti-infective agents

ABSTRACT

Seryl-lysyl-based peptide and peptidomimetic compounds are described as inhibitors of the enzyme N-myristoyl transferase to provide selective control of the fungal organism  Candida albicans . Peptidomimetic compounds of particular interest are those of the formula:                    
     wherein R 1  is selected form aminoalkyl, p-aminoalkylphenylalkyl, imidazolylalkylphenylalkyl, 2-alkylimidazolylalkylphenylalkyl, benzimidazolylalkylphenylalkyl and 2-alkylbenzimidazolylalkylphenylalkyl; wherein R 2  is selected from hydrido, alkyl, cycloalkyl, akenyl, alkynyl, haloalkyl, benzyl, alkylphenylalkyl, alkoxyphenylalkyl, halophenylalkyl, phenethyl, cycloalkylalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, alkoxycycloalkylalkyl and naphthylalkyl; wherein Y is selected from carboxylic acid, hydroxamic acid, phosphonic acid and tetrazolyl; or a pharmaceutically-acceptable salt, amide or ester thereof. Compounds of the formula are species-specific inhibitors of  C. albicans  with little effect on human NMT enzyme and thus would.be useful in treating  C. albicans  fungal infections in humans.

This is a continuation of application Ser. No. 08/823,101 filed on Mar. 24, 1997, now U.S. Pat. No. 5,942,600 which is a continuation of application Ser. No. 08/450,607 filed on May 25, 1995, which is now abandoned.

FIELD OF THE INVENTION

Compounds and methods are known for control of pathogenic fungi. Of particular interest herein are certain peptidomimetic compounds useful to inhibit the enzyme N-myristoyl transferase which, in turn, is useful for selective control of the fungal organism Candida albicans.

BACKGROUND OF THE INVENTION

Candida albicans, a diploid asexual yeast, is a major cause of systemic fungal infections, particularly in patients with acquired immunodeficiency syndrome (AIDS).

Species of the genus Candida are part of the normal human flora and are the most common yeast pathogens. Candida albicans, a dimorphic, asexual yeast, is the most frequently identified pathogen among Candida species. Systemic Candida infections commonly occur in patients who have been immunocompromised by treatment with immunosuppressive medication and broad spectrum antibiotics.

At the present time, therapy for a patient afflicted with systemic C. albicans infection is treatment with amphotericin B alone or in combination with the nucleoside analog 5-fluorocytosine. Alternatively, lanosterol 14α-demethylase inhibitors such as the imidazole ketoconazole or the triazole fluconazole are used. While amphotericin B is an effective fungicidal agent, it is nephrotoxic, does not penetrate into the cerebrospinal fluid, and must be given intravenously. Ketoconazole and the newer azoles are fungistatic rather than fungicidal.

A series of n-alkoxyacetic acids has been tested for effects on the growth of a variety of fungal species, including C. albicans, in Sabouraud dextrose agar, with 3-oxaundecanoic acid showing the broadest spectrum and highest potency and several other compounds, including 3-oxatetradecanoic acid, inhibiting growth [Gerson et al, J. Pharmaceut. Sci., 68, 82-84 (1979)].

U.S. Pat. No. 5,073,571 describes ether containing fatty acid compounds such as 13-oxatetradecanoic acid which have been evaluated as antiviral agents, e.g. against retroviruses such as HIV-1. The compound 13-oxatetradecanoic acid, which is a substrate for human acyl CoA synthetase and human myristoylCoA:protein N-myristoyltransferase (NMT), inhibits HIV-1 replication in acutely and chronically infected human T-lymphocyte cell lines at doses which do not cause cellular toxicity [B. Devadas et al, J. Biol. Chem., 267, 7224-7239 (1992)]. Studies with tritiated 13-oxatetradecanoic acid indicate that this fatty acid analog is incorporated into HIV-1 Pr55^(gag) and nef and some, but not all, cellular proteins [Bryant et al, Proc. Nat'l. Acad. Sci. USA, 88, 2055-2059 (1991)].

N-myristoylation of proteins is catalyzed by myristoylCoA:protein N-myristoyltransferase (NMT¹, N-myristoyltransferase). NMT transfers myristate (C14:0) from myristoylCoA to the amino-terminal Gly residue of proteins in such diverse eukaryotic species as animals, plants, and fungi [J. K. Lodge et al, J. Biol. Chem., 269, 2996-3000 (1994)]. This modification is required for the biological functions of a variety of cellular and viral proteins [D. R. Johnson et al, Ann. Rev. Biochem., in press, (1994)]. The NMT1 gene is essential for vegetative growth of S. cerevisiae. Moreover, haploid strains of S. cerevisiae containing a nmt1 null allele are not viable [R. J. Duronio et al, Proteins, Structure, Function, and Genetics, 13, 41-56 (1992c)]. Metabolic labeling studies indicate that S. cerevisiae produces at least 12 N-myristoylproteins during exponential growth [R. J. Duronio et al, J. Cell. Biol., 113, 1313-1330 (1991)]. Two functionally interchangeable ADP ribosylation factors, Arf1p and Arf2p, have been identified as N-myristoylproteins [T. Stearns et al, Mol. Cell. Biol., 10, 6690-6699 (1990)]. Metabolic labeling studies have shown that a laboratory strain of C.albicans (B311) synthesizes a small number of cellular N-myristoylproteins during exponential growth in rich media The C.albicans NMT gene has been isolated. Its 451 amino acid protein product shares 55% identity with the S. cerevisiae acyltransferase [R. C. Wiegand et al, J. Biol. Chem., 267, 8591-8598 (1992)]. Two ARF genes have also been indentified in C. albicans [C. A. Langner et al, J. Biol. Chem., 267, 17159-17169 (1992)]. At least one of them is a substrate for NMT [J. K. Lodge et al, J. Biol. Chem., 269, 2996-3000 (1994)]. Although C. albicans does not have a known sexual pathway, nonetheless it synthesizes a protein, Cag1, which is homologous to S. cervisiae Gpa1p [C. Sadhu et al, Mol. Cell. Biol., 12, 1977-1985 (1992)]. The amino termirnal sequence of Cag1 (GCGASVPVDD) makes it a likely substrate for S. cerevisiae Nmt1p [D. A. Towler et al, Ann. Rev. Biochem., 57, 69-99 (1988b)]. Moreover, CAG1 can complement the growth arrest and mating defects found in strains of S. cerevisiae with gpa1 null alleles [C. Sadhu et al, Mol. Cell. Biol., 12, 1977-1985 (1992)].

The peptide substrate specificities of C. albicans and S. cerevisiae NMTs are considerably different than that of human NMT [W. J. Rocque et al, J. Biol. Chem., 268, 9964-9971 (1993)]. However, surveys of a large panel of myristic acid analogs indicate that the acylCoA binding sites of the orthologous enzymes are quite similar [N. S. Kishore et al, J. Biol. Chem., 268, 4889-4902 (1993) footnote 2]. This apparent divergence in the peptide but not acylCoA binding sites undoubtedly reflects the similar requirements of these NMT enzymes for myristoylCoA and the marked differences in the numbers and types of protein substrates they must acylate in vivo [D. A. Rudnick et al, Adv. Enzvmol., 67, 375-430 (1993)].

Interaction between Saccharomyces-cerevisiae-derived myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) and photoactivatable ¹²⁵I-labeled octapeptides has been studied in the presence of other high-affinity peptide substrates and competitive inhibitors of such labeled octapeptides, such other peptide substrates and competitive inhibitors being the peptides GLYASKLS-NH₂ and ALYASKLS-NH₂, respectively [D. A. Rudnick et al, Proc. Natl. Acad. Sci., 90(3), 1087-1091 (1993)]

DESCRIPTION OF THE INVENTION

Peptidomimetic compounds, and pharmaceutical compositions thereof, for inhibition of the enzyme N-myristoyl transferase, provide selective control of the fungal organism Candida albicans, where such peptidomimetic compounds are selected from a class of compounds of Formula I:

wherein R¹ is selected from aminoalkyl, aminoalkylcycloalkyl, aminoalkylcycloalkylalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylaminocycloalkylalkyl, dialkylaminocycloalkylalkyl, aminoalkylarylalkyl, monoalkylaminoalkylarylalkyl, dialkylaminoalkylarylalkyl, aminocycloalkyl, monocycloalkylaminoalkyl, monoalkylaminocycloalkyl, monocycloalkylaminocycloalkyl, dialkylaminocycloalkyl, aminocycloalkylarylalkyl, aminoalkylarylcycloalkyl, aminocycloalkylarylcycloalkyl, monocycloalkylaminoalkylarylalkyl, monoalkylaminocycloalkylarylalkyl, monoalkylaminoalkylarylcycloalkyl, monocycloalkylaminocycloalkylarylalkyl, monocycloalkylaminoalkylarylcycloalkyl, monoalkylaminocycloalkylarylcycloalkyl, monocycloalkylaminocycloalkylarylcycloalkyl, dialkylaminocycloalkylarylalkyl, dialkylaminoalkylarylcycloalkyl, dialkylaminocycloalkylarylcycloalkyl, heterocyclic-A-alkyl, heterocyclic-A-alkylarylalkyl, heterocyclic-A-cycloalkyl, heterocyclic-A-cycloalkylarylalkyl, heterocyclic-A-alkylarylcycloalkyl, heterocyclic-A-cycloalkylarylcycloalkyl, heteroaryl-A-alkyl, heteroaryl-A-alkylarylalkyl, heteroaryl-A-cycloalkyl, heteroaryl-A-cycloalkylarylalkyl, heteroaryl-A-alkylarylcycloalkyl and heteroaryl-A-cycloalkylarylcycloalkyl, wherein A is either a covalent bond or is a moiety selected from

wherein R⁰ is selected from hydrido, alkyl, cycloalkyl and cycloalkylalkyl; wherein any foregoing heterocyclic-containing moiety may be fused to an aryl ring to form an arylheterocyclic moiety, and wherein any foregoing heteroaryl-containing moiety may be fused to an aryl ring to form an arylheteroaryl moiety, and wherein any of said heterocyclic moiety, heteroaryl moiety, arylheterocyclic moiety and arylheteroaryl moiety may be independently substituted at one or more substitutable positions with one or more radicals selected from halo, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, amino, aminoacyl, aminocarbonylalkoxy, monoalkylamino, dialkylamino, alkoxy, alkylthio, aralkyl and aryl, with the proviso that said heterocyclic moiety is selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl, and with the further proviso that said heteroaryl moiety is selected from imidazolyl and pyridinyl;

wherein R² is a radical selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, bicycloalkyl, alkenyl, cycloalkenyl, fused bicycloalkenyl, cycloalkyl fused to cycloalkenyl, alkenylalkyl, alkynyl, aralkyl and aryl, wherein any of said R² radicals having a substitutable position may be substituted by one or more radicals selected from alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, cycloalkenyl, fused bicycloalkenyl, cycloalkyl fused to cycloalkenyl, alkenylalkyl, alkynyl, halo, haloalkyl, alkoxy, alkoxyalkyl, alkylthio, aralkoxy, aryloxy, arylthio, aralkyl, aryl, alkoxycarbonyl, cycloalkoxycarbonyl, alkoxycarbonylalkyl and cycloalkoxycarbonylcycloalkyl;

wherein Y is an alkylol group or is an acidic group selected to contain at least one acidic hydrogen atom so as to impart a pKa less than about 5.0 to compound of Formula I;

or a pharmaceutically-acceptable ester, amide, or salt thereof.

Compounds of Formula I would be primarily useful in treating fungal infections caused by Candida albicans, particularly where selective inhibition of the NMT enzyme of this fungal organism is desirable over general NMT inhibition of the host, e.g., human subject. These compounds would also be useful as adjunctive therapies. For example, compounds of Formula I may be used in combination with other drugs, such as another anti-infective, e.g., metronidazole, to treat fungal infections.

The phrase “acidic group selected to contain at least one acidic hydrogen atom”, as used to define the —Y moiety, is intended to embrace chemical groups which, when attached at the “C-terminus” position of Formula I, confers acidic character to the compound of Formula I. “Acidic character” means proton-donor capability, that is, the capacity of the compound of Formula I to be a proton donor in the presence of a proton-receiving substance such as water. Typically, the acidic group should be selected to have proton-donor capability such that the product compound of Formula I has a PK_(a) in a range from about one to about six. More typically, the Formula I compound would have a pK_(a) in a range from about one to about five. An example of an acidic group containing at least one acidic hydrogen atom is carboxyl group (—COOH) attached directly to the “C-terminus” position. There are many examples of acidic groups other than carboxyl group, selectable to contain at least one acidic hydrogen atom. Such other acidic groups may be collectively referred to as “bioisosteres of carboxylic acid” or referred to as “acidic bioisosteres”. Specific examples of such acidic bioisosteres are described hereinafter. Compounds of Formula I may have one or more acidic protons and, therefore, may have one or more pKa values. It is preferred, however, that at least one of these pK_(a) values of the Formula I compound as conferred by the —Y moiety be in a range from about one to about five. The —Y moiety may be attached to the C-terminus position through any portion of the —Y moiety which results in a Formula I compound being relatively stable and also having a labile or acidic proton to meet the foregoing pK_(a) criteria. For example, where the —Y acid moiety is tetrazole, the tetrazole is attached at the ring carbon atom.

A class of preferred peptidomimetic compounds are those compounds of Formula II:

wherein R¹ is selected from aminoalkyl, aminoalkylcycloalkyl, aminoalkylcycloalkylalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylaminocycloalkylalkyl, dialkylaminocycloalkylalkyl, aminoalkylarylalkyl, monoalkylaminoalkylarylalkyl, dialkylaminoalkylarylalkyl, aminocycloalkyl, monocycloalkylaminoalkyl, monoalkylaminocycloalkyl, monocycloalkylaminocycloalkyl, dialkylaminocycloalkyl, aminocycloalkylarylalkyl, aminoalkylarylcycloalkyl, aminocycloalkylarylcycloalkyl, monocycloalkylaminoalkylarylalkyl, monoalkylaminocycloalkylarylalkyl, monoalkylaminoalkylarylcycloalkyl, monocycloalkylaminocycloalkylarylalkyl, monocycloalkylaminoalkylarylcycloalkyl, monoalkylaminocycloalkylarylcycloalkyl, monocycloalkylaminocycloalkylarylcycloalkyl, dialkylaminocycloalkylarylalkyl, dialkylaminoalkylarylcycloalkyl, dialkylaminocycloalkylarylcycloalkyl, heterocyclic-A-alkyl, heterocyclic-A-alkylarylalkyl, heterocyclic-A-cycloalkyl, heterocyclic-A-cycloalkylarylalkyl, heterocyclic-A-alkylarylcycloalkyl, heterocyclic-A-cycloalkylarylcycloalkyl, heteroaryl-A-alkyl, heeroaryl-A-alkylarylalkyl, heteroaryl- A-cycloalkyl, heteroaryl-A-cycloalkylarylalkyl, heteroaryl-A-alkylarylcycloalkyl and heteroaryl-A-cycloalkylarylcycloalkyl, wherein A is either a covalent bond or is a moiety selected from

wherein R⁰ is selected from hydrido, alkyl, cycloalkyl and cycloalkylalkyl; wherein any foregoing heterocyclic-containing moiety may be fused to an aryl ring to form an arylheterocyclic moiety, and wherein any foregoing heteroaryl-containing moiety may be fused to an aryl ring to form an arylheteroaryl moiety, and wherein any of said heterocyclic moiety, heteroaryl moiety, arylheterocyclic moiety and arylheteroaryl moiety may be independently substituted at one or more substitutable positions with one or more radicals selected from halo, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, amino, aminoacyl, aminocarbonylalkoxy, monoalkylamino, dialkylamino, alkoxy, alkylthio, aralkyl and aryl, with the proviso that said heterocyclic moiety is selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl, and with the further proviso that said heteroaryl moiety is selected from imidazolyl and pyridinyl;

wherein R² is a radical selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, bicycloalkyl, alkenyl, cycloalkenyl, fused bicycloalkenyl, cycloalkyl fused to cycloalkenyl, alkenylalkyl, alkynyl, aralkyl and aryl, wherein any of said R² radicals having a substitutable position may be substituted by one or more radicals selected from alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, cycloalkenyl, fused bicycloalkenyl, cycloalkyl fused to cycloalkenyl, alkenylalkyl, alkynyl, halo, haloalkyl, alkoxy, alkoxyalkyl, alkylthio, aralkoxy, aryloxy, arylthio, aralkyl, aryl, alkoxycarbonyl, cycloalkoxycarbonyl, alkoxycarbonylalkyl and cycloalkoxycarbonylcycloalkyl;

wherein Y is selected from hydroxyalkyl, hydroxycycloalkyl, hydroxycycloalkylalkyl, hydroxyaryl, hydroxyaminocarbonylaralkyl, hydroxyaminocarbonyl, hydroxyaminocarbonylalkyl, hydroxyaminocarbonylcycloalkyl, hydroxyaminocarbonylcycloalkylalkyl, hydroxyaminocarbonylaryl, carboxyl, carboxyalkyl, carboxycycloalkyl, carboxycyloalkylalkyl, tetrazolyl, tetrazolylalkyl, tetrazolylcycloalkyl, tetrazolylcycloalkylalkyl, phosphinic acid, monoalkylphosphinic acid, dialkylphosphinic acid, monocycloalkylphosphinic acid, dicycloalkylphosphinic acid, monocycloalkylalkylphosphinic acid, dicycloalkylalkylphosphinic acid, mixed monoalkylmonocycloalkylphosphinic acid, mixed monoalkylmonocycloalkylalkylphosphinic acid, mixed monocycloalkylmonocycloalkylalkylphosphinic acid, monoarylphosphinic acid, diarylphosphinic acid, mixed monoalkylmonoarylphosphinic acid, mixed monocycloalkylmonoarylphosphinic acid, mixed monocycloalkylalkylmonoarylphosphinic acid, phosphonic acid, alkylphosphonic acid, cycloalkylphosphonic acid, cycloalkylalkylphosphonic acid, aralkylphosphonic acid and arylphosphonic acid;

or a pharmaceutically-acceptable ester, amide, or salt thereof.

A more preferred class of peptidomimetic compounds consists of those compounds of Formula II wherein R¹ is selected from aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, aminoalkylphenylalkyl, monoalkylaminoalkylphenylalkyl, dialkylaminoalkylphenylalkyl, heterocyclicalkyl, heterocyclicalkylphenylalkyl, heteroarylalkyl, heteroarylalkylphenylalkyl, heterocycliccylcoalkyl, heterocycliccycloalkylalkyl, heteroarylcycloalkyl and heteroarylcycloalkylalkyl wherein any foregoing heterocyclic moiety may be fused to a phenyl ring to form a benzoheterocyclic moiety and wherein any foregoing heteroaryl moiety may be fused to a phenyl ring to form a benzoheteroaryl moiety, and wherein any of said heterocyclic moiety, benzoheterocyclic moiety, heteroaryl moiety and benzoheteroaryl moiety may be substituted at one or more substitutable positions with one or more radicals selected from halo, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkylthio, phenylalkyl and phenyl; with the proviso that said heterocyclic moiety is selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl, and with the further proviso that said heteroaryl is selected from imidazolyl and pyridinyl;

wherein R² is a radical selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl, wherein any of said R² radicals having a substitutable position may be substituted by one or more radicals selected from alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, halo, haloalkyl, alkoxy, alkylthio, phenylalkyl, phenyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, alkoxycarbonyl and alkoxycarbonylalkyl;

wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

wherein X is selected from alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl;

wherein R⁹ is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl;

or a pharmaceutically-acceptable ester, amide, or salt thereof.

An even more preferred class of peptidomimetic compounds consists of those compounds of Formula II wherein R¹ is selected from

wherein W is a divalent radical of the general structure

wherein W is selected from alkyl and cycloalkyl;

wherein each of R¹⁰ and R¹¹ is independently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl; wherein further R¹⁰ and R¹¹ may be taken together to form a saturated heterocyclic ring system having five or six ring members and having at least one nitrogen atom as a ring member and optionally having a second heteroatom selected from an oxygen, nitrogen or sulfur atom as a ring member, said heterocyclic ring system selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl; wherein each of R¹² and R¹³ is independently selected from hydrido, alkyl and haloalkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, halo, cycloalkyl, alkoxy, alkylthio, phenylalkyl and phenyl;

wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, phenylalkyl and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy;

wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

 with each of R⁴ through R⁸ independently selected from —CH₂—, —CH₂CH₂— and —CH₂CH₂CH₂—;

wherein R⁹ is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl;

or a pharmaceutically-acceptable ester, amide, or salt thereof.

A highly preferred class of peptidomimetic compounds consists of those compounds of Formula II wherein R¹ is selected from

wherein each of R¹⁰ and R¹¹ is independently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl; wherein further R¹⁰ and R¹¹ may be taken together to form a saturated heterocyclic ring system having five or six ring members and having at least one nitrogen atom as a ring member and optionally having a second heteroatom selected from an oxygen, nitrogen or sulfur atom as a ring member, said heterocyclic ring system selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl; wherein each of R¹² and R¹³ is independently selected from hydrido, alkyl and haloalkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, halo, cycloalkyl, alkoxy, alkylthio, phenylalkyl and phenyl;

wherein each of m, n, p and r is a whole number independently selected from 3 through 15; wherein each of q and t is a whole number independently selected from 1 through 6;

wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, phenylalkyl, and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy;

wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

 with each of R⁴ through R⁸ independently selected from —CH₂—, —CH₂CH₂— and —CH₂CH₂CH₂;

wherein R⁹ is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl and benzyl;

or a pharmaceutically-acceptable ester, amide, or salt thereof.

A more highly preferred class of peptidomimetic compounds consists of those compounds of Formula II wherein R¹ is selected from

wherein each of R¹⁰ and R¹¹ is independently selected from hydrido and alkyl; wherein further R¹⁰ and R¹¹ may be taken together to form a saturated heterocyclic ring system having five or six ring members and having at least one nitrogen atom as a ring member and optionally having a second hetero atom selected from an oxygen, nitrogen or sulfur atom as a ring member, said heterocyclic ring system selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl; wherein each of R¹² and R¹³ is independently selected from hydrido, alkyl and haloalkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, halo, cycloalkyl, alkoxy, alkylthio, phenylalkyl and phenyl;

wherein each of m, n, p and r is a whole number independently selected from 6 through 14; wherein each of q and t is a whole number independently selected from 3 through 6;

wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, phenylalkyl, and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy;

wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

 with each of R⁴ through R⁸ independently selected from —CH₂—, —CH₂CH₂— and —CH₂CH₂CH₂;

wherein R⁹ is selected from hydrido, alkyl and benzyl;

or a pharmaceutically-acceptable ester, amide, or salt thereof.

An even more highly preferred class of peptidomimetic compounds consists of those compounds of Formula II wherein R¹ is selected from

wherein each of R¹⁰ and R¹¹ is independently selected from hydrido and alkyl; wherein each of R¹² and R¹³ is independently selected from hydrido and alkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, alkoxy and alkylthio;

wherein each of m, n, p and r is a whole number independently selected from 6 through 14; wherein each of q and t is a whole number independently selected from 3 through 6;

wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, naphthylalkyl, phenylalkyl, and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy;

wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is —CH₂;

wherein R⁹ is selected from hydrido, alkyl and benzyl;

or a pharmaceutically-acceptable ester, amide, or salt thereof.

A very highly preferred class of peptidomimetic compounds consists of those compounds of Formula II wherein R¹ is selected from

H₂N(CH₂)₉—, H₂N(CH₂)₁₀—, H₂N(CH₂)₁₁—, CH₃NH(CH₂)₁₀—, (CH₃)₂N(CH₂)₁₀—, p-[H₂N(CH₂)₆]C₆H₄CH₂—, p-[H₂N(CH₂)₈]C₆H₄CH₂—, p-[H₂N(CH₂)₉]C₆H₄CH₂—, p-[H₂N(CH₂)₁₀]C₆H₄CH₂—, p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)—, p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)—, p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)—, p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)—,

wherein R² is selected from —H, —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH₂CH₂CH₃, —CH₂CH₂CH₂CH₂CH₂CH₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂CH₂CH(CH₃)₂, -cyclo-C₃H₅, -cyclo-C₄H₇, -cyclo-C₅H₉, -cyclo-C₆H₁₁, -Cyclo-C₇H₁₃, -cyclo-C₈H₁₅, —CH(CH₃)(CH₂CH₃), —CH(CH₂CH₃)₂, —CH(CH₃)(CH₂CH₂CH₃), —C(CH₃)₃, HC≡CCH₂—, H₂C═CH—, H₂C═CHCH₂—, —CH₂F, —CH₂C₆H₅, —CH₂C₆H₄-p-OCH₃, —CH₂C₆H₄-p-CH₃, —CH₂C₆H₄-p-F, —CH₂CH₂C₆H₅, —CH₂-cyclo-C₆H₁₁, —CH₂-cyclo-C₆H₁₀-4-F, —CH₂-cyclo-C₆H₁₀-4-CH₃, —CH₂-cyclo-C₆H₁₀-4-OCH₃, —-CH₂CH₂-cyclo-C₆H₁₁, —CH₂ -cyclo-C₅H₉, —CH₂CH₂-cyclo-C₅H₉ and —CH₂-2-naphthyl;

wherein Y is selected from —CO₂H, —CH₂CO₂H, —CONHOH, —PO₃H₂, and

or a pharmaceutically-acceptable ester, amide, or salt thereof.

A very highly preferred class of peptidomimetic compounds of Formula II of particular interest consists of compounds and their diastereoisomers of the group consisting of

L-Alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]oxopropyl]-L-seryl]-L-lysyl]-, (±), bis-trifluoroacetate;

L-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyllacetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate;

L-Alanine, 3-cyclohexyl-N-[[(11-amino-undecanoyl)-L-seryl]-L-lysyl]-, bis-trifluoroacetate;

L-Leucine, N-[[(11-amino-undecanoyl)-L-seryl]-L-lysyl]-, bis-trifluoroacetate;

L-Alanine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate;

L-Alanine, 3-phenyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate;

L-iso-Leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate;

L-Leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate;

Lysinamide, N-[1-cyclohexyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate;

Lysinamide, N-[1-cyclooctyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate; and

D-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate.

The term “hydridol” denotes a single hydrogen atom (H). This hydrido group may be attached, for example, to an oxygen atom to form a hydroxyl group; or, as another example, one hydrido group may be attached to a carbon atom to form a

group; or, as another example, two hydrido groups may be attached to a carbon atom to form a —CH₂— group. Where the term “alkyl” is used, either alone or within other terms such as “haloalkyl” and “hydroxyalkyl”, the term “alkyl” embraces linear or branched radicals having one to about twenty carbon atoms or, preferably, one to about twelve carbon atoms. More preferred alkyl radicals are “lower alkyl” radicals having one to about ten carbon atoms. Most preferred are lower alkyl radicals having one to about five carbon atoms. The term “cycloalkyl” embraces cyclic radicals having three to about ten ring carbon atoms, preferably three to about six carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term “haloalkyl”, embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with one or more halo groups, preferably selected from bromo, chloro and fluoro. Specifically embraced by the term “haloalkyl” are monohaloalkyl, dihaloalkyl and polyhaloalkyl groups. A monohaloalkyl group, for example, may have either a bromo, a chloro, or a fluoro atom within the group. Dihaloalkyl and polyhaloalkyl groups may be substituted with two or more of the same halo groups, or may have a combination of different halo groups. A dihaloalkyl group, for example, may have two fluoro atoms, such as difluoromethyl and difluorobutyl groups, or two chloro atoms, such as a dichloromethyl group, or one fluoro atom and one chloro atom, such as a fluoro-chloromethyl group. Examples of a polyhaloalkyl are trifluoromethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl and 2,2,3,3-tetrafluoropropyl groups. The term “difluoroalkyl” embraces alkyl groups having two fluoro atoms substituted on any one or two of the alkyl group carbon atoms. The terms “alkylol” and “hydroxyalkyl” embrace linear or branched alkyl groups having one to about ten carbon atoms any one of which may be substituted with one or more hydroxyl groups. The term “alkenyl” embraces linear or branched radicals having two to about twenty carbon atoms, preferably three to about ten carbon atoms, and containing at least one carbon-carbon double bond, which carbon-carbon double bond may have either cis or trans geometry within the alkenyl moiety. The term “alkynyl” embraces linear or branched radicals having two to about twenty carbon atoms, preferably two to about ten carbon atoms, and containing at least one carbon-carbon triple bond. The term “cycloalkenyl” embraces cyclic radicals having three to about ten ring carbon atoms including one or more double bonds involving adjacent ring carbons. The terms “alkoxy” and “alkoxyalkyl” embrace linear or branched oxy-containing radicals each having alkyl portions of one to about ten carbon atoms, such as a methoxy group. The term “alkoxyalkyl” also embraces alkyl radicals having two or more alkoxy groups attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl groups. The “alkoxy” or “alkoxyalkyl” radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkoxy or haloalkoxyalkyl.groups. The term “alkylthio” embraces radicals containing a linear or branched alkyl group, of one to about ten carbon atoms attached to a divalent sulfur atom, such as a methythio group. The term “aryl” embraces aromatic radicals such as phenyl, naphthyl and biphenyl. A preferred aryl group is phenyl. The term “aralkyl” embraces aryl-substituted alkyl radicals such as benzyl, diphenylmethyl, triphenylmethyl, phenylethyl, phenylbutyl and diphenylethyl. The terms “benzyl” and “phenylmethyl” are interchangeable. The terms “aryloxy” and “arylthio” denote radical respectively, aryl groups having an oxygen or sulfur atom through which the radical is attached to a nucleus, examples of which are phenoxy and phenylthio. The term “aralkoxy”, alone or within another term, embraces an aryl group attached to an alkoxy group to form, for example, benzyloxy. The term “alkenylalkyll” denotes a radical having a double-bond unsaturation site between two carbons, and which radical may consist of only two carbons or may be further substituted with alkyl groups which may optionally contain additional double-bond unsaturation. The term “acyl” whether used alone, or within a term such as acyloxy, denotes a radical provided by the residue after removal of hydroxyl from an organic acid, examples of such radical being acetyl and benzoyl. “Lower alkanoyl” is an example of a more prefered sub-class of acyl. A group embraced by the term “heterocyclic ring system” or “heteroaryl ring system”, or “heterocyclic”, or “heteroaryl” may be attached to the backbone of Formula I as a substituent at R¹ through a carbon atom of the hetero ring system, or may be attached through a carbon iatom of a moiety substituted on a hetero ring-member carbon atom. Also, such hetero-containing group may be attached through a ring nitrogen atom, where a bond is formable with such nitrogen atom. For any of the foregoing defined radicals, preferred radicals are those containing from one to about ten carbon atoms.

The term “monoalkylphosphinic acid” is intended to describe an acidic moiety having one alkyl group attached to the phosphorus atom through which alkyl group the phosphinic moiety is attached to the Formula I nucleus at “Y”. In such cases, this alkyl group will be “divalent” in character as shown below:

Another phospinic acid moiety described for use as “Y” substituent is characterized by the term “dialkylphosphinic acid” moiety, which term is intended to describe an acidic moiety having two alkyl groups attached to the phosphorous atom, one of such alkyl groups being “divalent” in character and through which this dialkylphosphinic acid moiety is attached at “Y”, as shown below:

The phrase “mixed monoalkylmonocycloalkylphosphinic acid” is intended to describe a phosphinic acid moiety having both a monoalkyl moiety and a monocycloalkyl moiety attached to the phosphorus atom, either of which may provide a “linking” divalent group to the nucleus of Formula I at the “Y” position.

Specific examples of alkyl groups are methyl, ethyl, n-propyl, isopropyl-, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, methylbutyl, dimethylbutyl and neopentyl. Typical alkenyl and alkynyl groups may have one unsaturated bond, such as an allyl group, or may have a plurality of unsaturated bonds, with such plurality of bonds either adjacent, such as allene-type structures, or in conjugation, or separated by several saturated carbons.

Also included in the family of compounds of Formula I, are isomeric forms including regioisomers, optical isomers, diastereoisomers and epimers, as well as the pharmaceutically-acceptable salts thereof. The term “pharmaceutically-acceptable salts” embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically-acceptable. Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula I may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, p-hydroxybenzoic, salicylic, phenylacetic, trifluoroacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, 2-hydroxyethanesulfonic, pantothenic, benzenesulfonic, toluenesulfonic, sulfanilic, mesylic, cyclohexylaminosulfonic, stearic, algenic, β-hydroxybutyric, malonic, galactaric and galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of Formula I include metallic salts made from aluminium, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these salts may be prepared by conventional means from the corresponding compound of Formula I by reacting, for example, the appropriate acid or base with the compound of Formula I.

Nomenclature used to define the peptides of Formula I is that specified by the IUPAC [published in European Journal of Biochemistry, 138, 9-37 (1984)], wherein conventional representation of the peptides stipulates that in a peptide sequence the amino group appears to the left and the carboxyl group to the right. When the amino acid has enantiomeric forms, it is the L form of the amino acid which is represented unless otherwise stated. In the amino acid structural formulas, each residue is generally represented by a single or 3-letter designation, corresponding to the trivial name of the amino acid in accordance with the following list:

TRIVIAL NAME SYMBOL ONE-LETTER SYMBOL Alanine Ala A Arginine Arg R Asparagine Asn N Aspartic Acid Asp D Cysteine Cys C Glutamine Gln Q Glutamic Acid Glu E Glycine Gly G Histidine His H Homocysteine Hcy — Isoleucine Ile I Leucine Leu L Lysine Lys K Methionine Met M Norvaline Nva — Penicillamine Pen — Phenylalanine Phe F Proline Pro P Serine Ser S Threonine Thr T Tryptophan Trp W Tyrosine Tyr Y Valine Val V Unspecified Amino Acid Xaa X

Another name for norvaline in n-propylglycine. The group ¹²⁵I-Tyr indicates a radioactive mono-iodinated tyrosine residue.

GENERAL SYNTHETIC SCHEMES

The compounds of the present invention represented by Formula I above can be prepared utilizing the following general procedures as schematically shown in Schemes I-VIII.

An appropriate DL-, D-, or L-lysine derivative 1 which has been differentially protected at both the alpha and omega amino groups with a suitable amine protecting group designated P₁ or P₂ is coupled to a suitably protected DL-, D-, or L-amino acid ester 2 containing an appropriate amino acid carboxyl-protecting group designated P₃ in a suitable solvent to produce a protected lysinamide of formula 3, wherein R², P₁, P₂, and P₃ are as defined above. Such reactions are well-known to those skilled in the art of solution-based peptide synthesis and generally employ methods such as those described by Bodanszky, M. and Bodanszky, A. in “The Practice of Peptide Synthesis” (1984), Springer-Verlag, New York, N.Y. or by Bodanszky, M. in “Principles of Peptide Synthesis” (1984), Springer-Verlag, New York, N.Y., and references cited therein.

Alternatively, the compounds of Formula I can be prepared according to Scheme I using well-known methods in solid-phase peptide synthesis such as those described by Barany, G. and Merrifield, R. B. in “The Peptides” (Gross, E. and Meienhofer, J., Eds.), vol.2, pp.1-284, (1979), Academic Press, New York, N.Y., and references cited therein. In this case, the carboxyl-protecting group designated P₃ is covalently attached, usually by an ester bond, to an appropriate solid phase resin, such as a hydroxymethyl-resin composed of styrene/1% divinylbenzene (Peninsula Laboratories) or an O-methlyphenylacetamidomethyl-resin (Sigma). Such resins are commercially available or can be readily prepared by one skilled in the art of solid-phase peptide synthesis.

Suitable amino protecting groups are well known in the art and include carbobenzoxy, 4-chloro-benzoxycarbonyl, t-butoxycarbonyl, and the like. P₁ and P₂ independently are selected from amine protecting groups, including but not limited to, aralkyl, substituted aralkyl, cycloalkenylalkyl, and substituted cycloalkenylalkyl, allyl, substituted allyl, acyl, alkoxy-carbonyl, aralkoxy-carbonyl and silyl. Examples of aralkyl include, but are not limited to benzyl, orthomethyl-benzyl, trityl and benzhydryl, which can be optionally substituted with halogen, alkyl of C₁-C₈, alkoxy, hydroxy, nitro, alkylene, amino, alkylamino, acylamino, and acyl, or their salts, such as phosphonium and ammonium salts. Examples of aryl groups include phenyl, naphthalenyl, indanyl, anthracenyl, durenyl, 9-phenylfluorenyl, and phenanthrenyl, cycloalkenylalkyl or substituted cycloalkenylalkyl radicals containing cycloalkyls of C₆-C₁₀. Suitable acyl groups include carbobenzoxy, 4-chloro-benzoxycarbonyl, t-butoxycarbonyl, iso-butoxycarbonyl, benzoyl, substituted benzoyl, butyryl, acetyl, trifluoroacetyl, trichloroacetyl, phthaloyl and the like.

One skilled in the art can choose appropriate combinations of P₁ and P₂. For example, a preferred amino protecting group for P₁ is carbobenzoxy and a preferred amino protecting group for P₂ is t-butoxycarbonyl. Alternatively, a preferred amino protecting group for P₁ is t-butoxycarbonyl and a preferred amino protecting group for P₂ is carbobenzoxy.

Additionally, the P₁ and/or P₂ protecting groups can form a heterocyclic ring with the nitrogen to which they are attached, for example, 1,2-bis-(methylene)benzene, phthalimidyl, succinimidyl, maleimidyl, and the like, and where these heterocyclic groups can further include adjoining aryl and cycloalkyl rings. In addition, the heterocyclic groups can be mon-. di-, or tri-substituted e.g., nitrophthalimidyl.

The term silyl refers to a silicon atom optionally substituted by one or more alkyl, aryl and aralkyl groups. Suitable silyl protecting groups include, but are not limited to trimethylsilyl, triethylsilyl, triisopropylsilyl, tert-butyl-dimethylsilyl, dimethylphenylsilyl, 1,2-bis(dimethylsilyl)benzene, 1,2-bis-(dimethylsilyl)ethane, and diphenylmethylsilyl.

Suitable carboxyl-protecting groups P₃ are well known in the art and include methyl, ethyl, benzyl, tertiary-butyl, 4-methoxyphenylmethyl, and the like.

The DL-, D-, or L-amino acid ester corresponding to formula 2 wherein R² and P₃ is as defined above are commercially available (Sigma Chemical Co.), or are readily prepared using standard methods well known in the art from readily available starting materials. Methods of preparing these amino acid derivatives from the corresponding amino acids are well known to those skilled in the art of organic chemistry including amino acid/amino acid ester chemistry using methods such as those described by R. M. Williams in “Synthesis of Optically Active α-Amino Acids,” (1989) Pergamon Press, New York, N.Y.

Standard coupling procedures can be used to couple the amino acids and amines. The carboxylic acid group is reacted to form an anhydride, mixed anhydride, acid halide, such as chloride or bromide, or active ester, such as esters of N-hydroxysuccinimide, HOBT (W. König, R. Geiger, Chem. Ber. 103, 788 (1970), and the like, using well known procedures and conditions. This reaction is usually facilitated by adding an acid scavenger such as a teritary amine base. Suitable acid scavengers include, but are not limited to triethylamine, tributylamine, tri-iso-propylamine, DBU, N-methylmorpholine, di-iso-propylethylamine, pyridine, 2,2,6,6-tetramethylpiperidine, N,N-dimethylaminopyridine, and the like, including mixtures of these bases. A preferred tertiary amine base is N-methylmorpholine. Appropriate solvent systems include tetrahydrofuran, ethylether, methyl-tert-butylether, methylene chloride, N,N-dimethylformamide, N,N-dimethylacetamide, and the like, including mixtures thereof.

Following preparation of the lysinamide drivative 3, the amino protecting group P₁ is removed under conditions which will not effect the remaining portion of the molecule to produce the lysinamide 4, where R², P₂, and P₃ are as defined above. These methods are well known in the art and include acid hydrolysis, hydrogenolysis and the like. A preferred method (W. H. Hartung, and R. Simonoff, Organic Reactions, 7, 263-326, (1953)) involves removal of the protecting group, e.g., removal of a carbobenzoxy group, by hydrogenolysis utilizing palladium on carbon in a suitable solvent system such as an alcohol, acetic acid, and the like or mixtures thereof. When the P₁ protecting group is a t-butoxycarbonyl group, it can be removed utilizing an inorganic or organic acid, e.g., HF, HCl or trifluoroacetic acid (H. Kappeler, and R. Schwyzer, Helv. Chim. Acta, 43, 1453, (1960)), in a suitable solvent system such as dioxane or methylene chloride. The resulting product is the lysine salt derivative.

Following neutralization of the salt, the amine 4 is then coupled to a suitably protected DL-, D-, or L-serine derivative 5, where P₄ is an appropriate hydroxyl-protecting group and P₁ is a suitable amino protecting group, as defined above, in an appropriate solvent to provide the desired protected serine-lysine dipeptide derivatives6, where R², P₁, P₂, P₃, and P₄ are as defined above. Examples of a suitable P₄ hydroxyl-protecting group include, but are not limited to tert-butyl and benzyl, and the like. In general, tert-butyl is preferred for P₄ under solution conditions, while benzyl is preferred for P₄ using solid phase synthetic methods.

Following preparation of the protected serine-lysine dipeptide 6, the amino protecting group P₁ is then removed under conditions that will not effect the rest of the molecule, using the general methods described above for the deprotection of 3, to provide the amine 7.

The resulting amine 7 is then coupled under standard conditions with an appropriate carboxylic acid 8, where R¹ is as defined above, in a suitable solvent to provide the protected amide 9. General procedures for the synthesis of these carboxylic acids 8 containing the appropriate R¹ groups are shown schematically in Schemes VII and VIII.

Following preparation of the protected amide 9, the carboxyl-protecting group P₃ is removed by base hydrolysis under standard conditions, using a solution of an appropriate metal hydroxide, such as lithium or sodium hydroxide, in an appropriate aprotic or protic solvent system such as an alcohol or water and the like or mixtures thereof, to provide the free carboxylic acid 10 after acidification. Alternatively, when P₃ is a benzyl or other aralkyl group, it may be removed by hydrogenolysis under standard conditions, using palladium on carbon in a suitable solvent system such as an alcohol, acetic acid, and the like or mixtures thereof. Alternatively, when P₃ is a tert-butyl group, it can be removed utilizing an organic or inorganic acid, e.g., HF, HCl or trifluoroacetic acid, in an appropriate solvent system such as dioxane or methylene chloride.

Following preparation of the protected carboxylic acid 10, the remaining P₂ and P₄ protecting groups can be removed under standard conditions as described above under conditions which do not effect the rest of the molecule to provide the deprotected dipeptide carboxylic acid derivatives 11. Alternatively, the sequence of reactions leading from 9 to 11 can be reversed, wherein the protecting groups P₂ and P₄ are removed first under conditions which do not effect the rest of the molecule, and then the carboxyl-protecting group P₃ can be removed subsequently, under suitable conditions as described above. Alternatively under solid phase conditions, the protecting group P₂ is removed first under conditions which do not effect the rest of the molecule, and then the carboxyl-protecting group P₃ and hydroxyl-protecting group P₄ can be removed subsequently, under suitable conditions using HF, as described above. In either case, the resulting final products 11 or their derivatives or salts can be crystallized or purified chromatographically using either a chiral or achiral column as is well known to those skilled in the art.

Alternatively, the sequence of coupling and deprotection reactions leading to intermediate 9 can be altered as depicted in Scheme II.

Starting from a suitable ε-amino protected lysine derivative 12, subsequent coupling to the protected serine derivative 5 produces the protected dipeptide 13, wherein P₁, P₂, P₃, and P₄ are as defined above. The amino protecting group P₁ in 13 is then removed under conditions which do not alter the rest of the molecule, and the resulting amine 14 is then coupled under standard conditions with 8 to provide 15. Subsequent removal from 15 of the carboxyl-protecting group P₃, usually by hydrolysis, provides the free carboxylic acid 16, which can be subsequently activated and coupled with 2 under standard conditions to provide intermediate 9, wherein R¹, R², P₂, P₃, and P₄ are as defined above. Similar methods to those described previously in the reactions in Scheme I can then be used to convert 9 to 11 under standard conditions.

Alternatively, as depicted in Scheme III, intermediate 16 can be activated and coupled under standard conditions with a suitably protected DL-, D-, or L-beta-amino acid ester 17 to provide the protected intermediate 18. Representative N-protected beta-amino acid esters are well known to those skilled in the art of amino acid ester chemistry and can be readily prepared using the methods described by E. Juaristi, D. Quintana and J. Escalante in Aldrichimica Acta, 27, 3-11 (1994), and references cited therein. Subsequent deprotection or hydrolysis removes the carboyl-protecting group P₃ from 18 to provide the free carboxylic acid derivative 19, which can be subsequently deprotected under the conditions described above for Scheme I to provide the homologated DL-, D-, or L-beta-amino acid analog 20.

Alternatively, intermediate 16 can be activated and coupled with a suitably protected phosphono-amino acid ester 21 to provide the coupled phosphonate ester product 22. Representative protected phosphono-amino acid esters 21 are well know to those skilled in the art of organophosphorus chemistry and can be readily prepared using the methods described by G. Osapay and A. Csiba in Eur. J. Med. Chem. 28, 355-61 (1993), R. G. Almquist, W.-R. Chao, and C. Jennings-White in J. Med. Chem. 28, 1064, (1985), T. Yokomatsu and S. Shibuya in Tetrahedron: Asymmetry, 3, 377-8 (1992), and M. C. Allen, W. Fuhrer, B. Tuck, R. Wade and J. M. Wood in J. Med. Chem. 32, 1652-61 (1989), and references cited therein. Subsequent hydrolysis removes the P₃ phosphonate-protecting groups from 22 to produce the phosphonic acids 23, which can be further deprotected under standard conditions as described previously to provide the fully-deprotected phosphonic acids 24.

Alternatively, intermediate 16 can be activated and coupled with a suitably N-protected tetrazole 25 to provide the coupled protected tetrazole product 26. Representative N-protected tetrazoles 25 are well known to those skilled in the art of amino acid chemistry and can be readily prepared from the corresponding protected aminoalkyl tetrazoles as described by Z. Grzonka, E. Bekowskas, and B. Liberek in Tetrahedron, 27, 1783 (1971), and by L. R. Hughes, J. Oldfield, S. J. Pegg, A. J. Barker and P. R. Marsham in European Patent EP 373891. Subsequent deprotection of 27 under standard conditions, as described previously, provides the fully deprotected tetrazoles 28.

Alternatively, intermediate ester 9 can be reacted with a suitably protected hydroxylamine derivative in a suitable solvent to provide the coupled hydroxyl-protected hydroxamic acid product 29, as described by E. W. Petrillo and M. A. Ondetti in U.S. Pat. No. 4,284,561 (1981). Representative oxygen-protected hydroxylamines are commercially available or readily prepared by those skilled in the art. Subsequent deprotection of 29 can be accomplished under standard conditions either stepwise through intermediate 30 or directly to provide the fully deprotected hydroxamic acid analogs 31.

The intermediate carboxylic acids 8 required for the syntheses depicted in Schemes I-VI are either commercially available or readily prepared by those skilled in the art of organic synthesis. Representative general procedures for the preparation of these intermediates 8 are depicted in Schemes VII and VIII.

Commercially available p-iodophenyl acetic acid 32 is esterified with an alcohol, preferably methanol, under standard conditions to provide the

corresponding methyl p-iodophenylacetate 33. The iodo-ester 33 is then coupled with an appropriate acetylenic alcohol 34 to provide the coupled alcohol product 35 under conditions utilizing a palladium catalyst as described by K. Sonogashira, Y. Tohda and N. Hagihara in Tetrahedron Letters, 50, 4467-70 (1975). This reaction may be applied to a variety of acetylenic alcohols where the number of methylene units defined by x may be varied between 1 and 9. The resulting unsaturated alcohol 35 is then reduced by hydrogenolysis in the presence of a suitable catalyst such as palladium on carbon to provide the saturated alcohol product 36, which can be cleanly converted to the corresponding saturated iodide 37, under standard conditions using known alcohol group manipulations.

The iodide ester 37 may be hydrolyzed with base to provide the corresponding free carboxylic acid 38, after acidification, which is then reacted with a suitable nitrogen heterocycle in the presence of base and in a suitable aprotic solvent to give the coupled carboxylic acid product 39, after acidification. Essentially any acid scavenger, such as sodium hydride or a tertiary amine as previously defined, may be used in this reaction. Sodium hydride is the preferred base. Examples of suitable heterocycles include, but are not limited to, 1,2,4-triazole, 1,2,3-triazole, imidazole, benzimidazole, 2-mercapto-pyridine, N-methyl-2-mercaptoimidazole, 2-mercaptobenzimidazole, or 1,2,4-triazole, 1,2,3-triazole, imidazole, or benzimidazole systems substituted with halo, alkyl or alkoxy groups. Preferably, the heterocycle is an imidazole or benzimidazole ring; most preferred is a 2-methylimidazole.

Alternatively, the iodide ester 37 can be converted stepwise to the corresponding amino ester 42 after formation and reduction of the corresponding azide intermediate 41. Amino ester 42 is then N-protected with a suitable amino protecting group, P₁, as defined above, to provide 43. Preferably, P₁ is a t-butoxycarbonyl (BOC) group, as depicted in Scheme VII. The resulting N-protected amino ester 43 is then hydrolyzed under standard conditions to give the N-protected amino acid 44, after acidification.

Alternatively as shown in Scheme VIII, the iodophenylacetate ester 33 can be alkylated α to the ester group with a suitable alkyl halide R′X in an aprotic solvent and in the presence of base such as sodium hydride to provide the racemic iodophenyl alkanoate esters 45. Preferably R′ is a primary lower alkyl group such as methyl. The resulting product 45 can then be carried through the same sequence of reactions as previously described for those in Scheme VII to provide the a-alkyl substituted intermediates 46-55.

The following is a description of preparation of a compound (Comparator Compound “A”) which is not part of the present invention. Following this synthesis description is a table of data obtained by evaluation of Comparator Compound “A” in accordance with the methods described in the “Biological Evaluation” section.

Preparation of D-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-D-seryl]-D-lysyl]-, bis-trifluoroacetate.

Part A:

To commercially available (Peninsula Laboratories) hydroxymethyl-resin of styrene/1% divinylbenzene (0.67 g, 0.75 mequiv/g) in 10 mL of dichloromethane was added N-BOC-(3-cyclohexyl)-D-alanine (0.55 g, 2.0 mmoles), dicyclohexylcarbodiimide (DCC, 0.4 g, 2.0 mmoles), and 4-dimethyl-aminopyridine (DMAP, 0.02 g, 0.2 mmoles). After stirring for 18 hours at room temperature, the amino acid-resin was separated by filtration and treated with 20 mL of 50% trifluoroacetic acid in dichloromethane for 30 minutes, and separated by filtration. The resulting amino acid-resin was washed sequentially with dichloromethane (3×20 mL), isopropanol (3×20 mL), diisopropylethylamine 10% (v/v) in dichloromethane (3×20 mL), and dichloromethane (3×20 mL).

Part B:

N-α-BOC-N-ε-(2-chloro-benzyloxycarbonyl)-D-lysine (0.83 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part A for 60 minutes at room temperature. The dipeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part C:

N-BOC-(O-benzyl)-D-serine (0.59 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part B for 60 minutes at room temperature. The tripeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part D:

To 4-[(2-methyl-1H-imidazol-1-yl)butyl]phenylacetic acid hydrochloride (0.08 g, 0.26 nmoles) in 2 mL of dimethylformamide (DMF) was added diisopropyl-ethylamine (0.04 mL, 0.26 mmoles). The resulting mixture was added to a suspension of the tripeptide-resin product from Part C in 5 mL of dichloromethane, followed by the addition of dicyclohexylcarbodiimide (0.05 g, 0.26 nmoles). After 18 hours at room temperature, the solvent was removed by filtration, and the resulting resin was washed with dichloromethane.

Part E:

The resin product from Part D was treated with 10 mL of 90% hydrogen fluoride in anisole (v/v) for 60 minutes at 0° C. The hydrogen fluoride was removed by evaporation, the resulting residue was extracted with 30% acetic acid in water and lyophilized. The crude material was purified by reverse phase HPLC on a Waters Deltapak RPC-18 column using a linear gradient of 1% to 35% acetonitrile (0.05% trifluoroacetic acid) in water (0.05% trifluoroacetic acid) over 30 minutes at 15 mL/min, which after lyophilization, gave 53 mg of 95% pure (by HPLC) D-alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-D-seryl]-D-lysyl]-, bis-trifluoroacetate; HRMS: (M+H) calcd. 641.4027, found 641.4038.

Amino acid analyses: theory obs. serine 1.00 0.98 lysine 1.00 1.02 D-cyclohexylalanine: observed but not quantitated. IC₅₀ IC₅₀ caEC₅₀ caNMT hNMT 24 hours (μM) (μM) Selectivity (μM) >1000 >1000 ND >400 caNMT = Candida albicans NMT; hNMT = human NMT; ca = Candida albicans ND = not determined.

The following procedures constitute specific exemplification of methods to prepare starting materials, intermediates and product compounds embraced by the foregoing General Synthetic Schemes. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare the compounds of the invention. All temperatures expressed are in degrees Centigrade.

EXAMPLE 1

Part A: Preparation of L-Alanine, 3-cyclohexyl-, Methyl Ester, Trifluroacetate.

To a solution of L-alanine, 3-cyclohexyl-N-BOC-, methyl ester (1.0 g, 3.5 mmol) in CH₂Cl₂ (4.00 mL), trifluoroacetic acid (1.00 mL) was added, and the mixture was stirred at room temperature for 1 hour. The trifluoroacetic acid was removed under reduced pressure, the residue was triturated with ether, and filtered. The solid material thus obtained was washed thoroughly with ether and dried in a dessicator under vacuum over NaOH pellets to give 0.87 g of L-alanine, 3-cyclohexyl-, methyl ester trifluroacetate, which was used without further purification in Part B.

Part B: Preparation of L-Alanine, 3-cyclohexyl-N-[N-α-Carbobenzoxy-N-ε-BOC-L-Lysyl]-, Methyl Ester.

N-α-Carbobenzoxy-N-ε-BOC-L-lysine (1.3 g, 3.4 mmol) and HOBt (0.6 g, 4.0 mmol) were dissolved in CH₂Cl₂ (8.00 mL) and dimethylacetamide (2.0 mL), and the solution was cooled to 0° C. To this cooled solution, DCC (0.74 g, 3.6 mmol) in CH₂Cl₂ (10 mL) was added dropwise, and the reaction was stirred at 0° C. for 1 hour, and filtered. The filtrate was added to a solution of the L-alanine, 3-cyclohexyl-, methyl ester trifluroacetate from Part A in CH₂Cl₂ (3.0 mL) containing N-methylmorpholine (0.37 g, 3.68 mmol). The resulting mixture was stirred at room temperature for 16 hours and concentrated under vacuum. The residue was partitioned between EtOAc (40 mL) and 5% citric acid (20 mL). The organic phase was washed successively with 5% citric acid (2×20 mL), water (2×20 mL), 0.25 N NaOH (2×20 mL), brine, dried (Na₂SO₄), and filtered. After the removal of the solvent, the product was crystallized from EtOAc/hexane to give 1.4 g (73%) of L-alanine, 3-cyclohexyl-N-[N-α-carbobenzoxy-N-ε-BOC-L-lysyl]]-, methyl ester as a pale yellow powder. FAB-MS m/z=554 (M+Li); HRMS calcd. for C₂₉H₄₅N₃O₇Li (M+Li) 554.3418, found 554.3447.

Part C: Preparation of L-Alanine, 3-cyclohexyl-N-[N-ε-BOC-L-Lysyl]-, Methyl Ester Acetate.

A solution of L-alanine, 3-cyclohexyl-N-[N-α-carbobenzoxy-N-ε-BOC-L-lysyl]]-, methyl ester (0.6 g, 1.1 mmol) from Part B in MeOH (15 mL) and acetic acid (0.07 mL) was hydrogenated at atmospheric pressure in the presence of 5% Pd/C (0.2 g) for 1 hour and filtered. The filtrate was concentrated under reduced pressure, and the resulting L-alanine, 3-cyclohexyl-N-[N-ε-BOC-L-lysyl]-, methyl ester acetate salt [FAB-MS: m/z=420 (M+Li)] was used without further purification in Part D.

Part D: Preparation of L-Alanine, 3-cyclohexyl-N-[[N-ε-BOC-L-Lysyl]-L-(O-t-butyl)-N-carbobenzoxy-seryl]-, Methyl Ester.

To a solution of N-carbobenzoxy-(O-t-butyl)-L-serine (0.4 g, 1.35 mmol) in dimethylacetamide (1 mL) and dichloromethane (5 mL) at 0° C., was added HOBt (0.23 g, 1.53 mmol) and DCC (0.3 g, 1.45 mmol), and the resulting mixture was stirred for 1 hour, then filtered. The filtrate was added to a solution of L-alanine, 3-cyclohexyl-N-[N-ε-BOC-L-lysyl]-, methyl ester acetate salt from Part C, in dimethylacetamide (1 mL) containing N-methyl-morpholine (0.14 g, 1.36 mmol), and the stirring was continued at room temperature for 16 hours. After the removal of the solvent in vacuo, the residue was partitioned between cold 0.25 N NaOH (25 mL) and EtOAc (25 mL). The organic phase was washed successively with cold 0.25 N NaOH (2×25 mL), water, 5% citric acid (2×15 mL), water, dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The resulting material was crystallized from EtOAc/hexane to give 0.48 g (63%) of L-alanine, 3-cyclohexyl-N-[[N-ε-BOC-L-lysyl]-L-(O-t-butyl)-N-carbobenzoxy-seryl]-, methyl ester as a white powder. FAB-MS m/z=697 (M+Li), 641, & 597. HRMS calcd. for C₃₆H₅₉N₄O₉ (M+H), 691.4282, found 691.4266.

Part E: Preparation of L-Alanine, 3-cyclohexyl-N-[N-ε-BOC-L-Lysyl]-L-(O-t-butyl)seryl]-, Methyl Ester.

A solution of L-alanine, 3-cyclohexyl-N-[[N-ε-BOC-L-lysyl]-L-(O-t-butyl)-N-carbobenzoxy-seryl]-, methyl ester from Part D (0.18 g, 0.26 mmol) in MeOH (10.0 mL) was hydrogenated at atmospheric pressure in the presence of 5% Pd/C (0.05 g) at room temperature for 1 hour. The catalyst was removed by filtration, the filtrate concentrated, and the residue dried in a desiccator for 1 hour to give L-alanine, 3-cyclohexyl-N-[N-ε-BOC-L-lysyl]-L-(O-t-butyl)seryl]-, methyl ester [FAB-MS m/z=563 (M+Li)], which was used without purification in Part M below.

Part F: Preparation of Methyl 4-iodophenylacetate.

4-iodophenylacetic acid (5.2 g, 0.02 mol) and DMAP (0.25 g, 0.002 mol) was dissolved in dichloromethane (40 mL) and methanol (3.2 mL), and the solution was cooled to 0° C. Then a solution of DCC (4.32 g, 0.021 mol) in dichloromethane was added dropwise over a period of 15 minutes. The reaction mixture was stirred at 0° C. for 1 hour and at room temperature for 16 hours, then filtered. The filtrate was diluted with dichloromethane (40 mL) and washed with 5% citric acid (4×25 mL), water (2×50 mL), dried (Na₂SO₄), filtered, and concentrated. The residual liquid was purified by silica gel flash column chromatography eluting with 20% EtOAc in hexane to give methyl 4-iodophenylacetate (4.5 g, 82%) as a colorless liquid: ¹H-NMR (CDCl₃) δ: 7.64 (d, 2H, J=8.4 Hz), 7.01 (2H, J=8.4 Hz), 3.69 (s, 3H), 3.57 (s, 2H); FAB-MS m/z=283 (M+Li). HRMS calcd. for C₉H₁₀IO₂ (M+H), 276.9725, found 276.9726.

Part G: Preparation of Methyl±2-(4-iodophenyl)propionate.

To a solution of methyl 4-iodophenylacetate (1.0 g, 3.62 mmol) in dry THF (10 mL) was added sodium hydride (0.095 g, 3.96 mmol, 80% suspension), stirring continued at 5° C. for 30 minutes, followed by the addition of iodomethane (0.68 g, 4.8 mmol). After stirring for 2 hours at room temperature, additional iodomethane (0.46 g, 3.2 mmol) was added, and the reaction mixture was stirred at room temperature overnight for 16 hours. Acetic acid (0.2 mL) was added, and the reaction mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc (30 mL) and 5% citric acid (25 mL). The organic phase was washed with water (2×20 mL), dried (Na₂SO₄), filtered and concentrated. The resulting substance was purified by silica gel flash column chromatography eluting with 20% EtOAc in hexane to give methyl±2-(4-iodophenyl)propionate (0.7 g, 70%) as a pale yellow liquid. ¹H-NMR (CDCl₃) δ: 7.64 (d, 2H, J=8.4 Hz), 7.03 (2H, J=8.4 Hz), 3.66 (m over s, 4H), 1.46 (d, 3H, J=7.2 Hz); FAB-MS m/z=291 (M+H); HRMS calcd for C₁₀H₁₂IO₂ (M+H) 290.9882, found 290.9861.

Part H: Preparation of Methyl±2-[4-(4-hydroxy-1-butynyl)phenyl]-propionate.

To a mixture of methyl±2-(4-iodophenyl)propionate (0.9 g, 3.1 mmol), butyn-1-ol (0.4 g, 5.7 mmol), and triethylamine (0.43 g, 4.3 mmol) in acetonitrile (15 mL) at 0° C. was added bistriphenylphosphine palladium chloride (0.2 g, 0.28 mmol) and CuI (0.025,g). The reaction mixture was stirred at 0° C. under argon atmosphere for 30 minutes and at room temperature for 2.5 hours. The dark colored reaction mixture was concentrated under reduced pressure, and the residue was partitioned between 5% citric acid (50 mL) and EtOAc (50 mL). The organic phase was washed with 5% citric acid (3×15 mL), water, dried (Na₂SO₄), filtered, and concentrated. The resulting material was purified by silica gel flash column chromatography eluting with 40% EtOAc in hexane to afford methyl±2-[4-(4-hydroxy-1-butynyl)phenyl]propionate (0.69 g, 96%) as an orange colored liquid. FAB-MS m/z=233 (M+H); HRMS calcd for C₁₄H₁₇O₃ (M+H) 233.1178, found 233.1149.

Part I: Preparation of Methyl±2-[4-(4-hydroxybutyl)phenyl]propionate.

Methyl±2-[4-(4-hydroxy-1-butynyl)phenyl]propionate (0.6 g, 2.31 mmol) was dissolved in MeOH (10 mL) and hydrogenated at 40 psi for 4.5 hours in the presence of 5% Pd/C (0.3 g) and filtered. The filtrate was concentrated to dryness to give methyl±2-[4-(4-hydroxybutyl)phenyl]propionate (0.6 g, 98%) as a pale yellow viscous liquid. FAB-MS m/z=237 (M+H); HRMS calcd for C₁₄H₂₁O₃ (M+H) 237.1491, found 237.1491.

Part J: Preparation of Methyl±2-[4-(4-iodobutyl)phenyl]propionate.

To a solution of methyl±2-[4-(4-hydroxybutyl)phenyl]propionate (0.8 g, 3.4 mmol) in acetonitrile (15 mL) was added methyltriphenoxyphosphonium iodide (2.0 g, 4.4 mmol), and the mixture was stirred at room temperature for 16 hours. Methanol (5 mL) was added, and the reaction mixture was concentrated under reduced pressure. The resulting residue was partitioned between cold 0.25 N NaOH (50 mL) and dichloromethane (50 mL), the organic phase was washed with 0.25 N NaOH (2×25 mL), water (3×25 mL) dried (Na₂SO₄), filtered, and concentrated. The residual material was purified by silica gel flash column chromatography eluting with 20% EtOAc in hexane to furnish methyl±2-[4-(4-iodobutyl)phenyl]propionate (1.0 g, 85%) as a pale yellow viscous liquid. ¹H NMR (CDCl₃) δ: 7.2 (m, 2H), 7.14 (m, 2H), 3.66 (s over m, 4H), 3.2 (t, 2H), 2.6 (t, 2H), 1.85 (m, 2H), 1.7 (m, 2H), 1.48 (d, 3H, J=7.2 Hz); FAB-MS m/z=353 (M+Li); HRMS calcd for C₁₄H₂₀IO₂ (M+H) 347.0508, found 347.0509.

Part K: Preparation of ±2-[4-(4-iodobutyl)phenyl]propionic Acid.

A solution of methyl±2-[4-(4-iodobutyl)phenyl]propionate (1.0 g, 2.9 mmol) in 1M LiOH (5.00 mL) containing MeOH (3.75 mL) was heated to 60° C. for 1 hour under a nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure, water (25 mL) was added and the mixture was extracted with ether (3×15 mL). The combined ether extracts were washed with water (3×15 mL), dried (Na₂SO₄), filtered, and concentrated to give ±2-[4-(4-iodobutyl)phenyl]propionic acid (0.7 g, 73%) as a colorless liquid. ¹H NMR (CDCl₃) δ: 7.22 (m, 2H), 7.15 (m, 2H), 3.7 (m, 1H), 3.4 & 3.2 (t, 2H), 2.6 (t, 2H), 1.85 (m, 2H), 1.7 (m, 2H), 1.5 (d, 3H, J=6.9 Hz); FAB-MS m/z=339 (M+Li).

Part L: Preparation of ±2-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]-propionic Acid Hydrochloride.

To a solution of ±2-[4-(4-iodobutyl)phenyl]propionic acid (0.25 g, 0.75 mmol) in DMF (1.5 mL) at 0° C. was added NaH (0.95 g, 80% suspension, 2.1 mmol), and the mixture was stirred at 0° C. for 30 minutes and at room temperature for 1.5 hours under an argon atmosphere. The DMF was distilled away in vacuo. The resulting residue was treated with 2N HCl (3 mL) and water (10 ml) and washed with EtOAc (3×5 mL). The aqueous phase was freeze dried and the residue was washed with 10% CH₃CN in EtOAc (20 mL) and dried to afford ±2-[[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]propionic acid hydrochloride (0.14 g, 58%). ¹H-NMR (DMSO-d6) δ: 7.64 (d, 1H, J=2.1 Hz), 7.54 (d, 1H, J=2.1 Hz), 7.15 (m, 4H), 4.1 (t, 2H, J=7.2 Hz), 3.6 (q, 1H), 2.57 (s over m, 5H), 1.75 (m, 2H), 1.55 (m, 2H), 1.32 (d, 3H, J=6.9 Hz); FAB-MS m/z=287 (M+H); HRMS calcd for C₁₇H₂₃N₂O₂ (M+H) 287.1760, found 287.1754.

Part M: Preparation of L-Alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]oxopropyl]-L-(Q-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, (±), Methyl Ester.

The ±[2-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]]propionic acid hydrochloride (0.12 g, 0.38 mmol) from Part L and HOBt (0.065 g, 0.43 mmol) were dissolved in dimethylacetamide (1.00 mL) and dichloromethane (1.00 mL). The mixture was cooled to 0° C., DCC (0.08 g, 0.39 mmol) was added, stirred for 45 minutes, then added to a solution of L-alanine, 3-cyclohexyl-N-[N-ε-BOC-L-lysyl]-L-(O-t-butyl) seryl]-, methyl ester from Part E in dimethylacetamide (0.5 mL) containing N-methylmorpholine (0.028 g, 0.27 mmol) and DMAP (0.005 g). The reaction mixture was stirred at room temperature for 16 hours, and concentrated in vacuo. The resulting residue was partitioned between dichloromethane (25 mL) and cold 0.25 N NaOH (10 mL). The organic phase was washed successively with cold 0.25 N NaOH (10 mL), water (3×10 mL), dried (Na₂SO₄), filtered, and concentrated. The resulting solid was washed with cold 15% ethyl acetate in hexane and dried to give 0.14 g (65%) of L-alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]-phenyl]-oxopropyl]-L-(O-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, (±), methyl ester as an amorphous material, which was used without further purification in Part N. FAB-MS m/z=825 (M+H), HRMS calcd for C₄₅H₇₃N₆O₈Li (M+Li): 831.5572, found 831.5597.

Part N: Preparation of L-Alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]oxopropyl]-L-(O-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, (±), bis-trifluoroacetate.

A solution of L-alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]-oxopropyl]-L-(O-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, (±), methyl ester from Part M (0.14 g, 0.17 mmol) in 1M LIOH (0.4 mL, 0.4 mmol) and THF (0.3 mL) was stirred at room temperature for 2.5 hours. The reaction mixture was diluted with water (20 mL) and washed with EtOAc (2×20 mL). The aqueous phase was acidified with 5% citric acid, and extracted with dichloromethane (2×15 mL). The combined organic phases were washed with water (2×10 mL), dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue, which contained the desired L-alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl)-1H-imidazol-1-yl)butyl]phenyl]-oxopropyl]-L-(O-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, (±), [FAB-MS m/z=811 (M+H), HRMS calcd. for C₄₄H₇₁N₆O₈ (M+H), 811.5333, found 811.5328], was treated with trifluoroacetic acid (0.8 mL) and stirred at room temperature for 3.5 hours. After the removal of trifluoroacetic acid under reduced pressure, the residue was purified by reverse phase HPLC using a 5-70% CH₃CN/H₂0 gradient (30 min) at a flow rate of 70 mL/min. The appropriate fractions were pooled and freeze dried to give 0.035 g (23%) of pure L-alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]-oxopropyl]-L-seryl]-L-lysyl]l-, (±), bis-trifluoroacetate as a white powder. FAB-MS m/z=655 (M+H); HRMS calcd for C₃₅H₅₅N₆O₈ (M+H): 655.4183, found 655.4210. Amino acid analyses: calcd serine 1.00, lysine 1.00; found serine 1.00, lysine 1.00.

EXAMPLE 2

Part A: Preparation of Methyl 4-(4-Hydroxy-1-butynyl)phenylacetate.

To a solution of butyn-1-ol (0.76 g, 0.11 mol) and methyl 4-iodophenylacetate (1.5 g, 0.0054 mol) in acetonitrile (10 mL) at 0° C., triethylamine (1.5 mL, 0.01 mol) was added, followed by the addition of bistriphenylphosphine palladium chloride (0.25 g, 0.36 mmol) and CuI (0.025 g). The reaction mixture was stirred at 0° C. under an argon atmosphere for 30 minutes and at room temperature for 3 hours. The dark colored reaction mixture was concentrated under reduced pressure, and the residue was partitioned between 5% citric acid (50 mL) and EtOAc (50 mL). The organic phase was washed with 5% citric acid (3×15 mL), water, dried (Na₂SO₄), filtered, and concentrated. The resulting material was purified by silica gel flash column chromatography eluting with 35% EtOAc in hexane to afford methyl 4-(4-hydroxy-1-butynyl)phenylacetate (1 g, 85%) as a dark colored liquid. FAB-MS m/z=219 (M+H), HRMS calcd. for C₁₃H₁₅O₃ (M+H), 219.1021, found 219.1008. Calcd for C₁₃H₁₄O₃: C, 71.54, H 6.46; found: C, 71.04, H, 6.41.

Part B: Preparation of Methyl 4-(4-Hydroxy-1-butyl)phenylacetate.

Methyl 4-(4-hydroxy-1-butynyl)phenylacetate (10.6 g, 0.0485 mol) was dissolved in methanol (200 mL), then 10% palladium on carbon (1.1 g) was added, and the mixture was stirred under hydrogen (50 psi). After 6 hours, additonal 10% palladium on carbon (1 g) was added, and the mixture was stirred overnight. The catalyst was filtered through celite, the filtrate was concentrated and dried in vacuo to give 10.20 g (94.5%) of methyl 4-(4-hydroxy-1-butyl)phenylacetate as a yellow liquid. FAB-MS m/z=223 (M+H); HRMS calcd for C₁₃H₁₉O₃ (M+H) 223.1334, found 223.1328.

Part C: Preparation of Methyl 4-(4-Iodo-1-butyl)phenylacetate.

To a solution of methyl 4-(4-hydroxy-1-butyl)phenylacetate (3.88 g, 17 mmol) in dry acetonitrile (10 mL), a solution of methyl triphenoxyphosphonium iodide (10.26 g, 23 mmol) in dry acetonitrile (100 mL) was added, and the reaction was stirred at 0° C. The reaction mixture was warmed up to room temperature over several hours and stirred at room temperature overnight. The reaction mixture was quenched with excess methanol at 0° C. The solvents were removed under reduced pressure, the residue was dissolved in ethyl acetate (500 mL), and washed successively with cold 0.2N NaOH (2×500 mL), water (2×500 mL), saturated brine (2×500 mL), dried over MgSO₄, filtered, and concentrated. The crude material thus obtained was purified by silica gel flash column chromatography eluting with 10% EtOAc in hexane to give 4.12 g (71%) of pure methyl 4-(4-iodo-1-butyl)phenylacetate as a clear liquid. ¹H NMR (400 MHz, CDCl₃) δ: 1.70-1.89 (m, 4H), 2.62 (t, 2H, J=7.52 Hz), 3.20 (t, 2H, J=6.86 Hz), 3.60 (s, 2H), 3.69 (s, 3H), 7.17 (ab quartet, 4H, J=7.92 Hz). FAB-MS m/z=333 (M+H); HRMS calcd for C₁₃H₁₈O₂I (M+H) 333.0351, found 333.0347.

Part D: Preparation of 4-(4-Iodo-1-butyl)phenylacetic Acid.

Methyl 4-(4-iodo-1-butyl)phenylacetate (21.28 g, 0.064 mol) was dissolved in methanol (160 mL). Lithium hydroxide (6.72 g, 0.16 mol) and water (10 mL) were added, and the reaction mixture was stirred for 18 hours at room temperature. The solvents were removed under reduced pressure, the residue was treated with ethyl acetate (600 mL), and the organic solution was washed with 1N HCl (3×300 mL), brine (3×300 mL), dried over MgSO₄, and filtered. The filtrate was concentrated and dried in vacuo to give 17.5 g (85.9%) of 4-(4-iodo-1-butyl)phenylacetic acid as a yellow solid. ¹H NMR (300 MHz, CD₃OD) δ: 1.68-1.84 (m, 4H), 2.61 (t, 2H, J=7.35 Hz), 3.24 (t, 2H, J=6.75 Hz), 3.55 (s, 2H), 7.16 (ab quartet, 4H, J=8.26 Hz). FAB-MS m/z=319 (M+H); HRMS calcd for C₁₂H₁₆O₂I (M+H) 319.0194, found 319.0208.

Part E: Preparation of [[4-[4-(2-Methyl-1H-imidazol-1-yl]-butyl]-phenylacetic Acid Hydrochloride.

To a suspension of sodium hydride (3.17 g, 0.132 mol) in dry DMF (30 mL) at 5° C., a solution of 2-methylimidazole (10.11 g, 0.123 mol) in dry DMF (50 mL) was added. The reaction mixture was stirred for 30 minutes at 5° C., then a solution of 4-(4-iodo-1-butyl)phenylacetic acid (14 g, 0.044 mol) was added in dry DMF (15 mL), and stirring continued for 1.5 hours. The reaction mixture was allowed to warm to room temperature and stirred for 5 hours, cooled to 0° C., and quenched with 1N HCl. The solution was concentrated, the residue dissolved in water, and washed several times with ethyl acetate. Water was removed under reduced pressure, the residue was dried in vacuo, and treated with ethyl acetate/acetonitrile (1:1, v/v). The solid was filtered, and washed with ethyl acetate several times. The solid thus obtained was then washed with absolute ethanol. The ethanol washings were concentrated and dried to give 7.63 g (64%) of 4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]-phenylacetic acid hydrochloride. ¹H NMR (300 MHz, CD₃OD) δ: 1.65-1.88 (m, 4H), 2.58 (s, 3H), 2.67 (t, 2H, J=7.35 Hz), 3.56 (s, 2H), 4.12 (t, 2H, J=7.25 Hz), 7.17 (ab quartet, 4H, J=8.16 Hz), 7.40 (d, 1H, J=2.01 Hz), 7.47 (d, 1H, J=2.01 Hz). FAB-MS m/z=273 (M+H); HRMS calcd for C₁₆H₂₁N₂O₂ (M+H): 273.1603, found 273.1635.

Part F: Preparation of L-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-Methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(Q-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, Methyl Ester.

To a solution of 4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenylacetic acid hydrochloride (0.12 g, 0.39 mmol) and HOBt (0.065 g, 0.43 mmol) in dimethylacetamide (2.5 mL), DCC (0.085 g, 0.41 mmol) was added, and the mixture was stirred at 0° C. for 2 hours. Then a solution of L-alanine, 3-cyclohexyl-N-[N-ε-BOC-L-lysyl]-L-(O-t-butyl)seryl]-, methyl ester in dimethylacetamide (0.5 mL) containing N-methylmorpholine (0.041 g, 0.41 mmol) and DMAP (0.005 g) was added. The reaction mixture was stirred at room temperature for 24 hours, and concentrated in vacuo. The residue was partitioned between EtOAc (25 mL) and cold 0.25 N NaOH (10 mL). The organic phase was washed with water (3×15 mL), dried (Na₂SO₄), filtered, and concentrated under reduced pressure to give an amorphous substance which was crystallized from ether/hexane to afford 0.15 g (65%) of L-alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]-acetyl]-L-(O-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, methyl ester as a pale yellow powder. FAB-MS m/z=811 (M+H), HRMS calcd. for C₄₄H₇₁N₆O₈ (M+H), 811.5337, found 811.5324.

Part G: Preparation of L-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-Methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate.

The L-alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(O-t-butyl)seryl]-N-ε-BOC-L-lysyl]-, methyl ester (0.15 g, 0.19 mmol) from Part F, was stirred with 1 M LiOH, (0.3 mL) containing MeOH (0.2 mL), for 2 hours at room temperature. The mixture was acidified with 5% citric acid and extracted with EtOAc (3×15 mL). The combined organic phases were washed with water (3×10 mL), dried (Na₂SO₄), filtered, and concentrated. The resulting residue was dried in vacuo for 16 hours and then treated with trifluoroacetic acid (1.5 mL). After stirring for 4 hours at room temperature, the solution was concentrated under reduced pressure, and the residue was purified by reverse-phase HPLC using a 5-70% CH₃CN/H₂O gradient (30 min) at 70 mL/min flow rate. The appropriate fractions were combined and freeze dried to afford 0.053 g (34%) of L-alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]-phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate as a white powder. FAB-MS m/z=641 (M+H), HRMS calcd. for C₃₄H₅₃N₆O₆ (M+H), 641.4027, found 641.4041. Amino acid analyses: calcd for serine 1.00, lysine 1.00, found serine 1.02; lysine 1.00.

EXAMPLE 3

Part A:

To commercially available (Peninsula Laboratories) hydroxymethyl-resin of styrene/1% divinylbenzene (0.67 g, 0.75 mequiv/g) in 10 mL of dichloro-methane was added N-BOC-(3-cyclohexyl)-L-alanine (0.55 g, 2.0 mmoles), dicyclohexylcarbodiimide (0.4 g, 2.0 mmoles), and 4-dimethylaminopyridine (0.02 g, 0.2 nmoles). After stirring for 18 hours at room temperature, the amino acid resin was separated by filtration and treated with 50% trifluoroacetic acid in dichloromethane for 30 minutes. Then the amino acid resin was again separated by filtration, and was washed with dichloro-methane (3×20 mL), isopropanol (3×20 mL), diisopropylethylamine (10%, v/v) in dichloromethane (3×20 mL), and dichloromethane (3×20 mL).

Part B:

N-α-BOC-N-ε-(2-chloro-benzyloxycarbonyl)-L-lysine (0.83 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part A for 60 minutes. The dipeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid, and the resulting resin was washed as described in Part A.

Part C:

N-BOC-(O-benzyl)-L-serine (0.59 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part B for 60 minutes at room temperature. The tripeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part D:

N-BOC-11-aminoundecanoic acid (Bachem, 0.60 g, 2.0 mmoles) was activated with disuccinimidylcarbonate (0.56 g, 2.2 mmoles) and 4-dimethylamino-pyridine (0.02 g, 0.2 mmoles) in dimethylformamide/pyridine (2/1, v/v) and reacted with the resin product from Part C for 60 minutes at room temperature. The resulting resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was treated with 90% hydrogen fluoride/anisole (v/v) for 60 minutes at 0° C. The hydrogen fluoride was removed by evaporation, and the product was extracted into 30% acetic acid/water and then lyophilized. The crude material was purified by reverse phase HPLC on a Waters Deltapak RPC-18 column using a linear gradient of 1% to 35% acetonitrile (0.05% trifluoroacetic acid) in water (0.05% trifluoroacetic acid) over 30 minutes at 15 mL/min, which after lyophilization, gave 137 mg of 95% pure (by HPLC) L-alanine, 3-cyclohexyl-N-[[(il-amino-undecanoyl)-L-seryl]-L-lysyl]-, bis-trifluoroacetate. HRMS: (M+H) calcd 570.4231, found 570.4262. Amino acid analyses: calcd serine 1.00, lysine 1.00; found: serine 0.99, lysine 1.01.

EXAMPLE 4

Part A:

Commercially available (Sigma) N-BOC-L-leucyl-O-methylphenylacetamido-methyl-resin (1.0 g, 0.5 mmoles Leu/g; resin: polystyrene/1% divinylbenzene) was treated with 20 mL of 50% trifluoroacetic acid in dichloromethane for 30 minutes. The amino acid-resin was then separated by filtration, and washed with dichloromethane (3×20 mL), isopropanol (3×20 mL), diisopropylethyl-amine (10%, v/v) in dichloromethane (3×20 mL), and dichloromethane (3×20 mL).

Part B:

N-α-BOC-N-ε-(2-chloro-benzyloxycarbonyl)-L-lysine (0.83 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part A for 60 minutes at room temperature. The dipeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part C:

N-BOC-(O-benzyl)-L-serine (0.59 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part B for 60 minutes at room temperature. The tripeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane and the resulting resin was washed as described in Part A.

Part D:

N-BOC-11-aminoundecanoic acid (Bachem, 0.60 g, 2.0 mmoles) was activated with disuccinimidylcarbonate (0.56 g, 2.2 mmoles) and 4-dimethylamino-pyridine (0.02 g, 0.2 mmoles) in 10 mL of dimethylformamide/pyridine (2/1, v/v) and reacted with the resin product from Part C for 60 minutes at room temperature. The resulting resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was treated with 90% hydrogen fluoride/anisole (v/v) for 60 minutes at 0° C. The hydrogen fluoride was removed by evaporation, and the product was extracted into 30% acetic acid/water and then lyophilized. The crude material was purified by reverse phase HPLC on a Waters Deltapak RPC-18 column using a linear gradient of 1% to 35% acetonitrile (0.05% trifluoroacetic acid) in water (0.05% trifluoroacetic acid) over 30 minutes at 15 mL/min, which after lyophilization, gave 84.8 mg of 98% pure (by HPLC) L-leucine, N-[[(11-amino-undecanoyl)-L-seryl]-L-lysyl]-, bis-trifluoroacetate.

HRMS: (M+H) calcd 530.3918, found 530.3919. Amino acid analyses: calcd serine 1.00, lysine 1.00, leucine 1.00; found: serine 1.05, lysine 1.00, leucine 1.05.

EXAMPLE 5

Part A:

To commercially available (Peninsula Laboratories) hydroxymethyl-resin of styrene/1% divinylbenzene (0.22 g, 0.75 mequiv/g) in 10 mL of dichloro-methane was added N-BOC-L-alanine (0.035 g, 0.183 mmoles), dicyclohexyl-carbodiimide (0.034 g, 0.167 mmoles), and 4-dimethylaminopyridine (0.007 g, 0.06 mmoles). After stirring for 18 hours at room temperature, the amino acid-resin was separated by filtration, treated with 10 mL of 50% trifluoroacetic acid in dichloromethane for 30 minutes, and separated by filtration. The resulting amino acid-resin was washed with dichloromethane (3×10 mL), isopropanol (3×10 mL), diisopropylethylamine (10%, v/v) in dichloromethane (3×10 mL), and dichloromethane (3×10 mL).

Part B:

N-α-BOC-N-ε-(2-chloro-benzyloxycarbonyl)-L-lysine (0.83 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part A for 60 minutes at room temperature. The dipeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part C:

N-BOC-(O-benzyl)-L-serine (0.59 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part B for 60 minutes at room temperature. The tripeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part D:

To 4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenylacetic acid hydrochloride (0.053 g, 0.17 mmoles) in 2 mL of dimethylformamide/dichloromethane (1/1) was added diisopropylethylamine (0.03 mL, 0.17 nmoles). The mixture was then added to a suspension of the tripeptide-resin product from Part C in 5 mL of dichloromethane, followed by dicyclohexylcarbodiimide (0.034 g, 0.17 mmoles). After 18 hours at room temperature, the solvent was removed by filtration and the resulting resin was washed with dichloromethane.

Part E:

The resin product from part D was treated with 3 mL of 90% hydrogen fluoride in anisole (v/v) for 60 minutes at 0° C. The hydrogen fluoride was removed by evaporation, and the product was extracted into 30% acetic acid/water and then lyophilized. The crude material was purified by reverse phase HPLC on a Waters Deltapak RPC-18 column using a linear gradient of 1% to 35% acetonitrile (0.05% trifluoroacetic acid) in water (0.05% trifluoro-acetic acid) over 30 minutes at 15 mL/min, which after lyophilization, gave 16.7 mg of 99% pure (by HPLC) L-alanine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate. HRMS: (M+H) calcd 559.3244, found 559.3254. Amino acid analyses: calcd serine 1.00, lysine 1.00, alanine 1.00; found: serine 0.99, lysine 0.99, alanine 1.01.

EXAMPLE 6

Part A:

To commercially available (Peninsula Laboratories) hydroxymethyl-resin of styrene/1% divinylbenzene (0.22 g, 0.75 mequiv/g) in 10 mL of dichloro-methane was added N-BOC-L-phenylalanine (0.048 g, 0.183 mmoles), dicyclohexylcarbodiimide (0.034 g, 0.167 mmoles), and 4-dimethylamino-pyridine (0.007 g, 0.06 mmoles). After stirring for 18 hours at room temperature, the amino acid-resin was separated by filtration and treated with 10 mL of 50% trifluoroacetic acid in dichloromethane for 30 minutes, then again separated by filtration. The resulting amino acid-resin was washed with dichloromethane (3×10 mL), isopropanol (3×10 mL), diisopropylethylamine (10%, v/v) in dichloromethane (3×10 mL), and dichloromethane (3×10 mL).

Part B:

N-α-BOC-N-ε-(2-chloro-benzyloxycarbonyl)-L-lysine (0.83 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloro-methane and coupled to the resin product from Part A for 60 minutes at room temperature. The dipeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part C:

N-BOC-(O-benzyl)-L-serine (0.59 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 nmoles) in dichloromethane and coupled to the resin product from Part B for 60 minutes at room temperature. The tripeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part D:

To 4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenylacetic acid hydrochloride (0.053 g, 0.17 mmoles) in 2 mL of dimethylformamide/dichloromethane (1/1) was added diisopropylethylamine (0.03 mL, 0.17 mmoles). The mixture was then added to a suspension of the tripeptide-resin from Part C in 5 mL of dichloromethane, followed by dicyclohexylcarbodiimide (0.034 g, 0.17 mmoles). After 18 hours at room temperature, the solvent was removed by filtration and the resulting resin product was washed with dichloromethane.

Part E:

The resin product from Part D was treated with 3 mL of 90% hydrogen fluoride/anisole (v/v) for 60 minutes at 0° C. The hydrogen fluoride was removed by evaporation, and the product was extracted into 30% acetic acid/water and then lyophilized. The crude material was purified by reverse phase HPLC on a Waters Deltapak RPC-18 column using a linear gradient of 1% to 35% acetonitrile (0.05% trifluoroacetic acid) in water (0.05% trifluoroacetic acid) over 30 minutes at 15 mL/min, which after lyophilization, gave 17.7 mg of 97% pure (by HPLC) L- alanine, 3-phenyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate. HRMS: (M+H) cal. 635.3557, found 635.3565. Amino acid analyses: calcd serine 1.00, lysine 1.00, phenylalanine 1.00; found: serine 1.02, lysine 1.02, phenylalanine 0.96.

EXAMPLE 7

Part A:

To commercially available (Peninsula Laboratories) hydroxymethyl-resin of styrene/1% divinylbenzene (0.22 g, 0.75 mequiv/g) in 10 mL of dichloro-methane was added N-BOC-L-isoleucine (0.042 g, 0.183 mmoles), dicyclohexylcarbodiimide (0.034 g, 0.167 mmoles), and 4-dimethylamino-pyridine (0.007 g, 0.06 mmoles). After stirring for 18 hours at room temperature, the amino acid-resin was separated by filtration and treated with 10 mL of 50% trifluoroacetic acid in dichloromethane for 30 minutes, then again separated by filtration. The resulting amino acid-resin was washed with dichloromethane (3×10 mL), isopropanol (3×10 mL), diisopropylethylamine (10%, v/v) in dichloromethane (3×10 mL), and dichloromethane (3×10 mL).

Part B:

N-α-BOC-N-ε-(2-chloro-benzyloxycarbonyl)-L-lysine (0.83 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloro-methane and coupled to the resin product from Part A for 60 minutes at room temperature. The dipeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part C:

N-BOC-(O-benzyl)-L-serine (0.59 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part B for 60 minutes at room temperature. The tripeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part D:

To 4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenylacetic acid hydrochloride (0.053 g, 0.17 mmoles) in 2 mL of dimethylformamide/dichloromethane (1/1) was added diisopropylethylamine (0.03 mL. 0.17 mmoles). The mixture was then added to a suspension of the tripeptide-resin from Part C in 5 mL of dichloromethane, followed by dicyclohexylcarbodiimide (0.034 g, 0.17 mmoles). After 18 hours at room temperature, the solvent was removed by filtration, and the resulting resin product was washed with dichloromethane.

Part E:

The resin product from Part D was treated with 3 mL of 90% hydrogen fluoride/anisole (v/v) for 60 minutes at 0° C. The hydrogen fluoride was removed by evaporation, and the product was extracted into 30% acetic acid/water and then lyophilized. The crude material was purified by reverse phase HPLC on a Waters Deltapak RPC-18 column using a linear gradient of 1% to 35% acetonitrile (0.05% trifluoroacetic acid) in water (0.05% trifluoroacetic acid) over 30 minutes at 15 mL/min, which after lyophilization, gave 5.4 mg of 95% pure (by HPLC) L-iso-leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate. ESMS: (M+H) m/z=601. Amino acid analyses: calcd serine 1.00, lysine 1.00, iso-leucine 1.00; found: serine 1.07, lysine 1.05, iso-leucine 0.88.

EXAMPLE 8

Part A: Preparation of L-Lysine, [N-ε-(Carbobenzoxy)]-N-α-(L-[N-BOC-(O-benzyl)seryl]]-, Methyl Ester.

A mixture of EDC (8.0 g, 41,73 mmol), HOBt (5.63 g, 41.73 mmol), N-BOC-(O-benzyl)-L-serine (12.45 g, 41.73 mmol) was stirred in DMF (300 mL) at room temperature for 2 hours. To this reaction mixture was added N-ε-(carbobenzoxy)-L-lysine-, methyl ester hydrochloride (13.80 g, 41.73 mmol), followed by triethylamine (5.81 mL), and the stirring was continued for 18 hours. The mixture was dissolved in dichloromethane (1 L), and the organic phase was washed with dilute hydrochloric acid (1N, 500 mL), saturated sodium bicarbonate (500 mL), and brine. The organic layer was dried (MgSO₄), filtered, and concentrated to afford 23 g of L-lysine, [N-ε-(carbobenzoxy)]-N-α-[L-[N-BOC-(O-benzyl)seryl]]-, methyl ester.

Part B: Preparation of L-Lysine, [N-ε-(Carbobenzoxy)]-N-α-[L- (O-benzyl)-seryl]-, Methyl Ester Hydrochloride.

HCl (4N) in dioxane (80 mL) was added to L-lysine, [N-ε-(carbobenzoxy)]-N-α-[L-[N-BOC-(O-benzyl)seryl]]-, methyl ester (23.0 g, 40.23 mmol) from Part A, and the mixture was stirred for 2 hours. The solvent was removed in vacuo, and the excess HCl was removed by evaporationg with toluene to afford 20.0 g of L-lysine, [N-ε-(carbobenzoxy)]-N-α-[L-(O-benzyl)-seryl]-, methyl ester hydrochloride.

Part C: Preparation of L-Lysine, N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-Methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-, Methyl Ester.

A mixture of 4-[(2-methyl-1H-imidazol-1-yl)butyl]phenylacetic acid hydrochloride (2.43 g, 7.878 nmol), HOBt (1.046 g, 7.878 mmol), EDC (1.51 g, 7.878 mmol) in DMF (100 mL) was stirred at room temperature for 1 hour. To this mixture, was added L-lysine, [N-ε-(carbobenzoxy)]-N-α-[L-(O-benzyl)-seryl]-, methyl ester hydrochloride from Part B (4.00 g, 7.878 mmol), followed by triethylamine (1.60 g, 15.75 mmol), and the stirring was continued for 18 hours. The DMF was removed by distillation in vacuo. The residue was dissolved in dichloromethane, washed with citric acid (100 mL), sodium bicarbonate (100 mL), brine, dried, filtered, and concentrated to afford 5.7 g of L-lysine, N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-, methyl ester as a solid.

Part D: Preparation of L-Lysine, N-ε-(Carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-,.

Lithium hydroxide (0.227 g, 9.458 mmol) was added to a solution of L-lysine, N-e-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-, methyl ester (4.55 g, 6.27 mmol) from Part C in methanol (150 mL) and water (10 mL), and the reaction mixture was stirred for 20 hours, then concentrated. The residue was dissolved in water and was neutralized with potassiun bisulfate (0.25 M) solution. The aqueous solution was extracted with dichloromethane, dried and concentrated to afford 4.2 g (94%) of L-lysine, N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-,.

Part E: Preparation of L-Leucine, N-[N²-[N-[[4-[4-(2-Methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-N-ε-(carbobenzoxy)-L-lysyl]-, Methyl Ester.

L-Lysine, N-e-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-, (0.46 g. 6.46 mmol), HOBT (0.089 g, 6.78 mmol), and EDC (0.13 g, 6.78 mmol) were dissolved in 15 mL of DMF. The solution was stirred for 40 minutes at room temperature. L-Leucine methyl ester (0.13 g, 7.11 mmol) was dissolved in 5 mL of DMF containing N-methylmopholine (0.20g, 1.94 mol) and then added to this solution. The reaction mixture was stirred overnight at room temperature, and the DMF was removed in vacuo. The concentrated residue was brought up in 150 mL of dichloromethane, and the organic phase was washed with saturated aqueous NaHCO₃ (2×100 mL), brine (2×100 mL), dried over MgSO₄, filtered and concentrated. The concentrated residue was purified by silica gel flash column chromatography eluting with 5% methanol in methylene chloride to give 0.27g (49.8%) of L-leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-N-ε-(carbobenzoxy)-L-lysyl]-, methyl ester as a white solid. FAB-MS m/z=839 (M+H). HRMS: calcd for C₄₇H₆₃N₆O₈ (M+H) 839.4707, found: 839.4706.

Part F: Preparation of L-Leucine, N-[N²-[N-[[4-[4-(2-Methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-N-ε-(carbobenzoxy)-L-lysyl]-,.

The L-leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-N-ε-(carbobenzoxy)-L-lysyl]-, methyl ester (0.17 g, 2.03 mmol) from Part E and lithium hydroxide (0.022 g, 5.24 mmol) were dissolved in methanol (5 mL) and water (0.5 mL). The reaction mixture was stirred overnight at room tempterature, and then quenched with 0.25 M KHSO₄ until the pH=3. The methanol and water were removed in vacuo, and the concentrated residue was pumped dry. The resulting white solid was washed with ethanol. The filterate was concentrated and pumped dry to give 0.18 g of L-leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]-phenyl]-acetyl]-L-(O-benzyl)-seryl]-N-ε-(carbobenzoxy)-L-lysyl]-, as a white foaming solid. FAB-MS m/z=825 (M+H). HRMS: calcd for C₄₆H₆₁N₆O₈ (M+H) 825.4551, found: 825.4561.

Part G: Preparation of L-Leucine, N-[N²-[N-[[4-[4-(2-Methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate.

The L-leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-N-ε-(carbobenzoxy)-L-lysyl]-, from Part F was dissolved in 10 mL of methanol. Palladium on carbon (100 mg) and 1N trifluoroacetic acid in water (0.1 mL) were added to this solution. The solution was then stirred under a hydrogen atmosphere (50 psi) for 16 hours. The reaction mixture was filtered through celite and washed with excess methanol. The filtrate was concentrated. The concentrated residue was purified by reverse phase HPLC using a linear gradient of 10% to 90% acetonitrile in water (each containing 0.1% trifluoroacetic acid) to give 22 mg (17.8%) of L-leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]-phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate as a pale yellow solid. HRMS: calcd for C₃₁H₄₈N₆O₆ 601.3714, found 601.3707.

EXAMPLE 9

Part A: Preparation of L-Lysinamide, N-[1-Cyclohexyl-2-carbomethoxyethyl]-N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]-acetyl]-L- (O- benzyl)-seryl]-, ±.

L-Lysine, N-e-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-, (150.0 mg, 0.21 mmol), 1-hydroxy-benzotriazole hydrate (31.1 mg, 0.21 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (40.1 mg, 0.21 mmol) were mixed in dimethylformamide (2.0 mL) at 0° C. for 15 minutes. N-Methylmorpholine (60.0 mg, 0.60 mmol) and methyl (R,S)-3-amino-3-cyclohexylpropionate (46 mg, 0.21 nmol) were added, and the solution was stirred at room temperature for 16 hours. The solvent was removed at reduced pressure, and the residue taken up in methanol (1.00 mL). The product was isolated as a waxy solid by preparative HPLC to give 136 mg (73%) of L-lysinamide, N-[1-cyclohexyl-2-carbomethoxyethyl]-N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-, ±. HRMS calcd for C₅₀H₆₇N₆O₈ (M+H) 879.5020, found 879.5030.

Part B: Preparation of Lysinamide, N-[1-Cyclohexyl-2-carbomethoxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate.

The L-lysinamide, N-[1-cyclohexyl-2-carbomethoxyethyl]-N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-, from Part A (89 mg, 0.101 mmol) was mixed in methanol (3.0 mL) with trifluoroacetic acid (60 μL). Then palladium on carbon (15 mg of 10%) was added, and the solution was stirred under an atmosphere of hydrogen (50 psi) at room temperature for 16 hours. The catalyst was removed by filtration though a 0.2 micron nylon mesh filter, and the filter was washed with methanol (2×3.0 mL). The solvent was removed at reduced pressure to afford 76.0 mg (88% yield) of lysinamide, N-[1-cyclohexyl-2-carbomethoxy-ethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate as an oil. HRMS calcd for C₃₅H₅₅N₆O₆ (M+H) 655.4183, found 655.4188.

Part C: Preparation of Lysinamide, N-[1-Cyclohexyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate.

The lysinamide, N-[1-cyclohexyl-2-(carbomethoxy)ethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate from Part B (50 mg, 0.056 mmol) was dissolved in methanol/water (3.0 mL, 5:1). Lithium hydroxide monohydrate (15 mg, 0.366 mmol) was added, and the solution mixed for 3 hours at room temperature. The solvent was removed at reduced pressure, and the residue taken up in methanol (1.0 mL) and trifluoroacetic acid (30 μL). The product was isolated as a semi-solid by preparative HPLC to give 37.4 mg (77%) of lysinamide, N-[1-cyclohexyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate. HRMS calcd for C₃₄H₅₃N₆O₆ (M+H) 641.4027, found 641.4067.

EXAMPLE 10

Part A: Preparation of L-Lysinamide, N-[1-Cyclooctyl-2-carbomethoxyethyl]-N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-, ±.

L-Lysine, N-E-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]acetyl]-L-(O-benzyl)-seryl]-, (156.0 mg, 0.21 mmol), 1-hydroxy-benzotriazole hydrate (31.1 mg, 0.21 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (40.1 mg, 0.21 mmol) were mixed in dimethylformamide (2.0 mL) at 0° C. for 15 minutes. Then N-methyl-morpholine (60.0 mg, 0.60 nmol) and methyl (R,S)-3-amino-3-cyclooctyl-propionate (46 mg, 0.21 mmol) were added, and the solution was stirred at room temperature for 16 hours. The solvent was removed at reduced pressure, and the residue taken up in methanol (1.00 mL) The product was isolated as a waxy solid by preparative HPLC to give 145 mg (76%) of L-lysinamide, N-[1-cyclooctyl-2-carbomethoxyethyl]-N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-, ±. HRMS calcd for C₅₂H₇₁N₆O₈ (M+H) 907.5333, found 907.5354.

Part B: Preparation of Lysinamide, N-[1-Cyclooctyl-2-carbomethoxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate.

The L-lysinamide, N-[1-cyclooctyl-2-carbomethoxyethyl]-N-ε-(carbobenzoxy)-[N-α-[N-[4-[4-(2-methyl-1H-imidazol-1-yl)-butyl]phenyl]-acetyl]-L-(O-benzyl)-seryl]-, ± from Part A (135.0 mg, 0.149 mmol) was mixed in methanol (3.0 mL) with trifluoroacetic acid (60 μL). Then palladium on carbon (15 mg of 10%) was added, and the solution was stirred under an atmosphere of hydrogen (50 psi) at room temperature for 16 hours. The catalyst was removed by filtration though a 0.2 micron nylon mesh filter. The filter was washed with methanol (2×3.0 mL). The solvent was removed at reduced pressure to afford 102.0 mg (74%) of lysinamide, N-[1-cyclooctyl-2-carbomethoxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate as an oil. HRMS calcd for C₃₇H₅₉N₆O₆ (M+H) 683.4496, found 683.4534.

Part C: Preparation of Lysinamide, N-[1-Cyclooctyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate.

The lysinamide, N-[1-cyclooctyl-2-carbo-methoxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate from Part B (45 mg, 0.049 mmol) was mixed in tetrahydrofuran/methanol/water (3.0 mL, 8:2:1). Lithium hydroxide monohydrate (15 mg, 0.366 mmol) was added, and the solution was mixed for 3 hours at room temperature. The solvent was removed at reduced pressure, and the residue taken up in methanol (1.0 mL) and trifluoroacetic acid (30 μL). The product was isolated as a semi-solid by preparative HPLC to give 26.3 mg (78%) of lysinamide, N-[1-cyclooctyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]-phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate. HRMS calcd for C₃₆H₅₇N₆O₆ (M+H) 669.4340, found 669.4342.

EXAMPLE 11

Part A:

To commercially available (Peninsula Laboratories) hydroxymethyl-resin of styrene/1% divinylbenzene (0.66 g, 0.75 mequiv/g) in 10 mL of dichloromethane was added N-BOC-(3-cyclohexyl)-D-alanine (0.55 g, 2.0 mmoles), dicyclohexylcarbodiimide (0.4 g, 2.0 mmoles), and 4-dimethyl-aminopyridine (0.02 g, 0.2 mmoles). After stirring for 18 hours at room temperature, the amino acid-resin was separated by filtration and treated with 20 mL of 50% trifluoroacetic acid in dichloromethane for 30 minutes, and again separated by filtration. The resulting amino acid-resin was washed sequentially with dichloromethane (3×20 mL), isopropanol (3×20 mL), diisopropylethylamine 10% (v/v) in dichloromethane (3 ×20 mL), and dichloromethane (3×20 mL).

Part B:

N-α-BOC-N-ε-(2-chloro-benzyloxycarbonyl)-L-lysine (0.83 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part A for 60 minutes at room temperature. The dipeptide-resin was separated by filtration, the N-α-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part C:

N-BOC-(O-benzyl)-D-serine (0.59 g, 2.0 mmoles) was activated with dicyclohexylcarbodiimide (0.20 g, 1.0 mmoles) in dichloromethane and coupled to the resin product from Part B for 60 minutes at room temperature. The tripeptide-resin was separated by filtration, the N-A-BOC group was removed with trifluoroacetic acid in dichloromethane, and the resulting resin was washed as described in Part A.

Part D:

To 4-[(2-methyl-1H-imidazol-1-yl)butyl]phenylacetic acid hydrochloride (0.04 g, 0.13 mmoles) in 2 mL of dimethylformamide/dichloromethane (1/1) was added diisopropylethylamine (0.02 mL, 0.13 mmoles). The resulting mixture was added to a suspension of one third of the tripeptide-resin product from Part C in 5 mL of dichloromethane, followed by the addition of dicyclohexyl-carbodiimide (0.05 g, 0.26 mmoles). After 18 hours at room temperature, the solvent was removed by filtration, and the resulting resin was washed with dichloromethane.

Part E:

The resin product from Part D was treated with 10 mL of 90% hydrogen fluoride in anisole (v/v) for 60 minutes at 0° C. The hydrogen fluoride was removed by evaporation, the resulting residue was extracted with 30% acetic acid in water and then lyophilized. The crude material was purified by reverse phase HPLC on a Waters Deltapak RPC-18 column using a linear gradient of 1% to 35% acetonitrile (0.05% trifluoroacetic acid) in water (0.05% trifluoroacetic acid) over 30 minutes at 15 mL/min, which after lyophilization, gave 11.4 mg of 95% pure (by HPLC) D-alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate; HRMS: (M+H) calcd. 641.4027, found 641.4046. Amino acid analyses: calcd serine 1.00, lysine 1.00; found: serine 1.00, lysine 1.00.

Using analagous starting materials, methods and procedures as described in the foregoing General Synthetic Schemes and in the specific preparations of Examples #1-11, the compounds of Example #12-2786, as shown in Table I, may be prepared.

TABLE I

Ex. No. R¹ R² Y 12 H₂N(CH₂)₉— -cyclo-C₄H₇ —CO₂H 13 H₂N(CH₂)₉— -cyclo-C₅H₉ —CO₂H 14 H₂N(CH₂)₉— -cyclo-C₆H₁₁ —CO₂H 15 H₂N(CH₂)₉— -cyclo-C₇H₁₃ —CO₂H 16 H₂N(CH₂)₉— -cyclo-C₈H₁₅ —CO₂H 17 H₂N(CH₂)₉— —CH(CH₃)(CH₂CH₃) —CO₂H 18 H₂N(CH₂)₉— —CH(CH₂CH₃)₂ —CO₂H 19 H₂N(CH₂)₉— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 20 H₂N(CH₂)₉— —C(CH₃)₃ —CO₂H 21 H₂N(CH₂)₉— HC≡CCH₂— —CO₂H 22 H₂N(CH₂)₉— H₂C═CH— —CO₂H 23 H₂N(CH₂)₉— H₂C═CHCH₂— —CO₂H 24 H₂N(CH₂)₉— —CH₂F —CO₂H 25 H₂N(CH₂)₉— —CH₂C₆H₅ —CO₂H 26 H₂N(CH₂)₉— —CH₂C₆H₄-p-OCH₃ —CO₂H 27 H₂N(CH₂)₉— —CH₂C₆H₄-p-CH₃ —CO₂H 28 H₂N(CH₂)₉— —CH₂C₆H₄-p-F —CO₂H 29 H₂N(CH₂)₉— —CH₂CH₂C₆H₅ —CO₂H 30 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₁ —CO₂H 31 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 32 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 33 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 34 H₂N(CH₂)₉— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 35 H₂N(CH₂)₉— —CH₂-cyclo-C₅H₉ —CO₂H 36 H₂N(CH₂)₉— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 37 H₂N(CH₂)₉— —CH₂-2-naphthyl —CO₂H 38 H₂N(CH₂)₉— —H —PO₃H₂ 39 H₂N(CH₂)₉— —CH₃ —PO₃H₂ 40 H₂N(CH₂)₉— —CH₂CH₃ —PO₃H₂ 41 H₂N(CH₂)₉— —CH₂CH₂CH₃ —PO₃H₂ 42 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₃ —PO₃H₂ 43 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 44 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 45 H₂N(CH₂)₉— —CH(CH₃)₂ —PO₃H₂ 46 H₂N(CH₂)₉— —CH₂CH(CH₃)₂ —PO₃H₂ 47 H₂N(CH₂)₉— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 48 H₂N(CH₂)₉— -cyclo-C₃H₅ —PO₃H₂ 49 H₂N(CH₂)₉— -cyclo-C₄H₇ —PO₃H₂ 50 H₂N(CH₂)₉— -cyclo-C₅H₉ —PO₃H₂ 51 H₂N(CH₂)₉— -cyclo-C₆H₁₁ —PO₃H₂ 52 H₂N(CH₂)₉— -cyclo-C₇H₁₃ —PO₃H₂ 53 H₂N(CH₂)₉— -cyclo-C₈H₁₅ —PO₃H₂ 54 H₂N(CH₂)₉— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 55 H₂N(CH₂)₉— —CH(CH₂CH₃)₂ —PO₃H₂ 56 H₂N(CH₂)₉— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 57 H₂N(CH₂)₉— —C(CH₃)₃ —PO₃H₂ 58 H₂N(CH₂)₉— HC≡CCH₂— —PO₃H₂ 59 H₂N(CH₂)₉— H₂C═CH— —PO₃H₂ 60 H₂N(CH₂)₉— H₂C═CHCH₂— —PO₃H₂ 61 H₂N(CH₂)₉— —CH₂F —PO₃H₂ 62 H₂N(CH₂)₉— —CH₂C₆H₅ —PO₃H₂ 63 H₂N(CH₂)₉— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 64 H₂N(CH₂)₉— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 65 H₂N(CH₂)₉— —CH₂C₆H₄-p-F —PO₃H₂ 66 H₂N(CH₂)₉— —CH₂CH₂C₆H₅ —PO₃H₂ 67 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 68 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 69 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 70 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 71 H₂N(CH₂)₉— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 72 H₂N(CH₂)₉— —CH₂-cyclo-C₅H₉ —PO₃H₂ 73 H₂N(CH₂)₉— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 74 H₂N(CH₂)₉— —CH₂-2-naphthyl —PO₃H₂ 75 H₂N(CH₂)₉— —H -5-Tet 76 H₂N(CH₂)₉— —CH₃ -5-Tet 77 H₂N(CH₂)₉— —CH₂CH₃ -5-Tet 78 H₂N(CH₂)₉— —CH₂CH₂CH₃ -5-Tet 79 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₃ -5-Tet 80 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 81 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 82 H₂N(CH₂)₉— —CH(CH₃)₂ -5-Tet 83 H₂N(CH₂)₉— —CH₂CH(CH₃)₂ -5-Tet 84 H₂N(CH₂)₉— —CH₂CH₂CH(CH₃)₂ -5-Tet 85 H₂N(CH₂)₉— -cyclo-C₃H₅ -5-Tet 86 H₂N(CH₂)₉— -cyclo-C₄H₇ -5-Tet 87 H₂N(CH₂)₉— -cyclo-C₅H₉ -5-Tet 88 H₂N(CH₂)₉— -cyclo-C₆H₁₁ -5-Tet 89 H₂N(CH₂)₉— -cyclo-C₇H₁₃ -5-Tet 90 H₂N(CH₂)₉— -cyclo-C₈H₁₅ -5-Tet 91 H₂N(CH₂)₉— —CH(CH₃)(CH₂CH₃) -5-Tet 92 H₂N(CH₂)₉— —CH(CH₂CH₃)₂ -5-Tet 93 H₂N(CH₂)₉— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 94 H₂N(CH₂)₉— —C(CH₃)₃ -5-Tet 95 H_(2N(CH) ₂)₉— HC≡CCH₂— -5-Tet 96 H₂N(CH₂)₉— H₂C═CH— -5-Tet 97 H₂N(CH₂)₉— H₂C═CHCH₂— -5-Tet 98 H₂N(CH₂)₉— —CH₂F -5-Tet 99 H₂N(CH₂)₉— —CH₂C₆H₅ -5-Tet 100 H₂N(CH₂)₉— —CH₂C₆H₄-p-OCH₃ -5-Tet 101 H₂N(CH₂)₉— —CH₂C₆H₄-p-CH₃ -5-Tet 102 H₂N(CH₂)₉— —CH₂C₆H₄-p-F -5-Tet 103 H₂N(CH₂)₉— —CH₂CH₂C₆H₅ -5-Tet 104 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₁ -5-Tet 105 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 106 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 107 H₂N(CH₂)₉— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 108 H₂N(CH₂)₉— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 109 H₂N(CH₂)₉— —CH₂-cyclo-C₅H₉ -5-Tet 110 H₂N(CH₂)₉— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 111 H₂N(CH₂)₉— —CH₂-2-naphthyl -5-Tet 112 H₂N(CH₂)₁₀— —H —CO₂H 113 H₂N(CH₂)₁₀— —CH₃ —CO₂H 114 H₂N(CH₂)₁₀— —CH₂CH₃ —CO₂H 115 H₂N(CH₂)₁₀— —CH₂CH₂CH₃ —CO₂H 116 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₃ —CO₂H 117 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 118 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 119 H₂N(CH₂)₁₀— —CH(CH₃)₂ —CO₂H 120 H₂N(CH₂)₁₀— —CH₂CH(CH₃)₂ —CONHOH 121 H₂N(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ —CO₂H 122 H₂N(CH₂)₁₀— -cyclo-C₃H₅ —CO₂H 123 H₂N(CH₂)₁₀— -cyclo-C₄H₇ —CO₂H 124 H₂N(CH₂)₁₀— -cyclo-C₅H₉ —CO₂H 125 H₂N(CH₂)₁₀— -cyclo-C₆H₁₁ —CO₂H 126 H₂N(CH₂)₁₀— -cyclo-C₇H₁₃ —CO₂H 127 H₂N(CH₂)₁₀— -cyclo-C₈H₁₅ —CO₂H 128 H₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) —CO₂H 129 H₂N(CH₂)₁₀— —CH(CH₂CH₃)₂ —CO₂H 130 H₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 131 H₂N(CH₂)₁₀— —C(CH₃)₃ —CO₂H 132 H₂N(CH₂)₁₀— HC≡CCH₂— —CO₂H 133 H₂N(CH₂)₁₀— H₂C═CH— —CO₂H 134 H₂N(CH₂)₁₀— H₂C═CHCH₂— —CO₂H 135 H₂N(CH₂)₁₀— —CH₂F —CO₂H 136 H₂N(CH₂)₁₀— —CH₂C₆H₅ —CO₂H 137 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ —CO₂H 138 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ —CO₂H 139 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-F —CO₂H 140 H₂N(CH₂)₁₀— —CH₂CH₂C₆H₅ —CO₂H 141 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ —CONHOH 142 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 143 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 144 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 145 H₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 146 H₂N(CH₂)₁₀— —CH₂-cyclo-C₅H₉ —CO₂H 147 H₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 148 H₂N(CH₂)₁₀— —CH₂-2-naphthyl —CO₂H 149 H₂N(CH₂)₁₀— —H —PO₃H₂ 150 H₂N(CH₂)₁₀— —CH₃ —PO₃H₂ 151 H₂N(CH₂)₁₀— —CH₂CH₃ —PO₃H₂ 152 H₂N(CH₂)₁₀— —CH₂CH₂CH₃ —PO₃H₂ 153 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₃ —PO₃H₂ 154 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 155 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 156 H₂N(CH₂)₁₀— —CH(CH₃)₂ —PO₃H₂ 157 H₂N(CH₂)₁₀— —CH₂CH(CH₃)₂ —PO₃H₂ 158 H₂N(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 159 H₂N(CH₂)₁₀— -cyclo-C₃H₅ —PO₃H₂ 160 H₂N(CH₂)₁₀— -cyclo-C₄H₇ —PO₃H₂ 161 H₂N(CH₂)₁₀— -cyclo-C₅H₉ —PO₃H₂ 162 H₂N(CH₂)₁₀— -cyclo-C₆H₁₁ —PO₃H₂ 163 H₂N(CH₂)₁₀— -cyclo-C₇H₁₃ —PO₃H₂ 164 H₂N(CH₂)₁₀— -cyclo-C₈H₁₅ —PO₃H₂ 165 H₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 166 H₂N(CH₂)₁₀— —CH(CH₂CH₃)₂ —PO₃H₂ 167 H₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 168 H₂N(CH₂)₁₀— —C(CH₃)₃ —PO₃H₂ 169 H₂N(CH₂)₁₀— HC≡CCH₂— —PO₃H₂ 170 H₂N(CH₂)₁₀— H₂C═CH— —PO₃H₂ 171 H₂N(CH₂)₁₀— H₂C═CHCH₂— —PO₃H₂ 172 H₂N(CH₂)₁₀— —CH₂F —PO₃H₂ 173 H₂N(CH₂)₁₀— —CH₂C₆H₅ —PO₃H₂ 174 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 175 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 176 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-F —PO₃H₂ 177 H₂N(CH₂)₁₀— —CH₂CH₂C₆H₅ —PO₃H₂ 178 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 179 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 180 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 181 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 182 H₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 183 H₂N(CH₂)₁₀— —CH₂-cyclo-C₅H₉ —PO₃H₂ 184 H₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 185 H₂N(CH₂)₁₀— —CH₂-2-naphthyl —PO₃H₂ 186 H₂N(CH₂)₁₀— —H -5-Tet 187 H₂N(CH₂)₁₀— —CH₃ -5-Tet 188 H₂N(CH₂)₁₀— —CH₂CH₃ -5-Tet 189 H₂N(CH₂)₁₀— —CH₂CH₂CH₃ -5-Tet 190 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₃ -5-Tet 191 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 192 H₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 193 H₂N(CH₂)₁₀— —CH(CH₃)₂ -5-Tet 194 H₂N(CH₂)₁₀— —CH₂CH(CH₃)₂ -5-Tet 195 H₂N(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ -5-Tet 196 H₂N(CH₂)₁₀— -cyclo-C₃H₅ -5-Tet 197 H₂N(CH₂)₁₀— -cyclo-C₄H₇ -5-Tet 198 H₂N(CH₂)₁₀— -cyclo-C₅H₉ -5-Tet 199 H₂N(CH₂)₁₀— -cyclo-C₆H₁₁ -5-Tet 200 H₂N(CH₂)₁₀— -cyclo-C₇H₁₃ -5-Tet 201 H₂N(CH₂)₁₀— -cyclo-C₈H₁₅ -5-Tet 202 H₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) -5-Tet 203 H₂N(CH₂)₁₀— —CH(CH₂CH₃)₂ -5-Tet 204 H₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 205 H₂N(CH₂)₁₀— —C(CH₃)₃ -5-Tet 206 H₂N(CH₂)₁₀— HC≡CCH₂— -5-Tet 207 H₂N(CH₂)₁₀— H₂C═CH— -5-Tet 208 H₂N(CH₂)₁₀— H₂C═CHCH₂— -5-Tet 209 H₂N(CH₂)₁₀— —CH₂F -5-Tet 210 H₂N(CH₂)₁₀— —CH₂C₆H₅ -5-Tet 211 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ -5-Tet 212 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ -5-Tet 213 H₂N(CH₂)₁₀— —CH₂C₆H₄-p-F -5-Tet 214 H₂N(CH₂)₁₀— —CH₂CH₂C₆H₅ -5-Tet 215 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ -5-Tet 216 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 217 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 218 H₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 219 H₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 220 H₂N(CH₂)₁₀— —CH₂-cyclo-C₅H₉ -5-Tet 221 H₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 222 H₂N(CH₂)₁₀— —CH₂-2-naphthyl -5-Tet 223 H₂N(CH₂)₁₁— —H —CO₂H 224 H₂N(CH₂)₁₁— —CH₃ —CO₂H 225 H₂N(CH₂)₁₁— —CH₂CH₃ —CO₂H 226 H₂N(CH₂)₁₁— —CH₂CH₂CH₃ —CO₂H 227 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₃ —CO₂H 228 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 229 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 230 H₂N(CH₂)₁₁— —CH(CH₃)₂ —CO₂H 231 H₂N(CH₂)₁₁— —CH₂CH(CH₃)₂ —CO₂H 232 H₂N(CH₂)₁₁— —CH₂CH₂CH(CH₃)₂ —CO₂H 233 H₂N(CH₂)₁₁— -cyclo-C₃H₅ —CO₂H 234 H₂N(CH₂)₁₁— -cyclo-C₄H₇ —CO₂H 235 H₂N(CH₂)₁₁— -cyclo-C₅H₉ —CO₂H 236 H₂N(CH₂)₁₁— -cyclo-C₆H₁₁ —CO₂H 237 H₂N(CH₂)₁₁— -cyclo-C₇H₁₃ —CO₂H 238 H₂N(CH₂)₁₁— -cyclo-C₈H₁₅ —CO₂H 239 H₂N(CH₂)₁₁— —CH(CH₃)(CH₂CH₃) —CO₂H 240 H₂N(CH₂)₁₁— —CH(CH₂CH₃)₂ —CO₂H 241 H₂N(CH₂)₁₁— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 242 H₂N(CH₂)₁₁— —C(CH₃)₃ —CO₂H 243 H₂N(CH₂)₁₁— HC≡CCH₂— —CO₂H 244 H₂N(CH₂)₁₁— H₂C═CH— —CO₂H 245 H₂N(CH₂)₁₁— H₂C═CHCH₂— —CO₂H 246 H₂N(CH₂)₁₁— —CH₂F —CO₂H 247 H₂N(CH₂)₁₁— —CH₂C₆H₅ —CO₂H 248 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-OCH₃ —CO₂H 249 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-CH₃ —CO₂H 250 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-F —CO₂H 251 H₂N(CH₂)₁₁— —CH₂CH₂C₆H₅ —CO₂H 252 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₁ —CO₂H 253 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 254 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 255 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 256 H₂N(CH₂)₁₁— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 257 H₂N(CH₂)₁₁— —CH₂-cyclo-C₅H₉ —CO₂H 258 H₂N(CH₂)₁₁— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 259 H₂N(CH₂)₁₁— —CH₂-2-naphthyl —CO₂H 260 H₂N(CH₂)₁₁— —H —PO₃H₂ 261 H₂N(CH₂)₁₁— —CH₃ —PO₃H₂ 262 H₂N(CH₂)₁₁— —CH₂CH₃ —PO₃H₂ 263 H₂N(CH₂)₁₁— —CH₂CH₂CH₃ —PO₃H₂ 264 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₃ —PO₃H₂ 265 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 266 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 267 H₂N(CH₂)₁₁— —CH(CH₃)₂ —PO₃H₂ 268 H₂N(CH₂)₁₁— —CH₂CH(CH₃)₂ —PO₃H₂ 269 H₂N(CH₂)₁₁— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 270 H₂N(CH₂)₁₁— -cyclo-C₃H₅ —PO₃H₂ 271 H₂N(CH₂)₁₁— -cyclo-C₄H₇ —PO₃H₂ 272 H₂N(CH₂)₁₁— -cyclo-C₅H₉ —PO₃H₂ 273 H₂N(CH₂)₁₁— -cyclo-C₆H₁₁ —PO₃H₂ 274 H₂N(CH₂)₁₁— -cyclo-C₇H₁₃ —PO₃H₂ 275 H₂N(CH₂)₁₁— -cyclo-C₈H₁₅ —PO₃H₂ 276 H₂N(CH₂)₁₁— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 277 H₂N(CH₂)₁₁— —CH(CH₂CH₃)₂ —PO₃H₂ 278 H₂N(CH₂)₁₁— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 279 H₂N(CH₂)₁₁— —C(CH₃)₃ —PO₃H₂ 280 H₂N(CH₂)₁₁— HC≡CCH₂— —PO₃H₂ 281 H₂N(CH₂)₁₁— H₂C═CH— —PO₃H₂ 282 H₂N(CH₂)₁₁— H₂C═CHCH₂— —PO₃H₂ 283 H₂N(CH₂)₁₁— —CH₂F —PO₃H₂ 284 H₂N(CH₂)₁₁— —CH₂C₆H₅ —PO₃H₂ 285 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 286 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 287 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-F —PO₃H₂ 288 H₂N(CH₂)₁₁— —CH₂CH₂C₆H₅ —PO₃H₂ 289 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 290 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 291 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 292 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 293 H₂N(CH₂)₁₁— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 294 H₂N(CH₂)₁₁— —CH₂-cyclo-C₅H₉ —PO₃H₂ 295 H₂N(CH₂)₁₁— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 296 H₂N(CH₂)₁₁— —CH₂-2-naphthyl —PO₃H₂ 297 H₂N(CH₂)₁₁— —H -5-Tet 298 H₂N(CH₂)₁₁— —CH₃ -5-Tet 199 H₂N(CH₂)₁₁— —CH₂CH₃ -5-Tet 300 H₂N(CH₂)₁₁— —CH₂CH₂CH₃ -5-Tet 301 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₃ -5-Tet 302 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 303 H₂N(CH₂)₁₁— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 304 H₂N(CH₂)₁₁— —CH(CH₃)₂ -5-Tet 305 H₂N(CH₂)₁₁— —CH₂CH(CH₃)₂ -5-Tet 306 H₂N(CH₂)₁₁— —CH₂CH₂CH(CH₃)₂ -5-Tet 307 H₂N(CH₂)₁₁— -cyclo-C₃H₅ -5-Tet 308 H₂N(CH₂)₁₁— -cyclo-C₄H₇ -5-Tet 309 H₂N(CH₂)₁₁— -cyclo-C₅H₉ -5-Tet 310 H₂N(CH₂)₁₁— -cyclo-C₆H₁₁ -5-Tet 311 H₂N(CH₂)₁₁— -cyclo-C₇H₁₃ -5-Tet 312 H₂N(CH₂)₁₁— -cyclo-C₈H₁₅ -5-Tet 313 H₂N(CH₂)₁₁— —CH(CH₃)(CH₂CH₃) -5-Tet 314 H₂N(CH₂)₁₁— —CH(CH₂CH₃)₂ -5-Tet 315 H₂N(CH₂)₁₁— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 316 H₂N(CH₂)₁₁— —C(CH₃)₃ -5-Tet 317 H₂N(CH₂)₁₁— HC≡CCH₂— -5-Tet 318 H₂N(CH₂)₁₁— H₂C═CH— -5-Tet 319 H₂N(CH₂)₁₁— H₂C═CHCH₂— -5-Tet 320 H₂N(CH₂)₁₁— —CH₂F -5-Tet 321 H₂N(CH₂)₁₁— —CH₂C₆H₅ -5-Tet 322 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-OCH₃ -5-Tet 323 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-CH₃ -5-Tet 324 H₂N(CH₂)₁₁— —CH₂C₆H₄-p-F -5-Tet 325 H₂N(CH₂)₁₁— —CH₂CH₂C₆H₅ -5-Tet 326 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₁ -5-Tet 327 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 328 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 329 H₂N(CH₂)₁₁— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 330 H₂N(CH₂)₁₁— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 331 H₂N(CH₂)₁₁— —CH₂-cyclo-C₅H₉ -5-Tet 332 H₂N(CH₂)₁₁— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 333 H₂N(CH₂)₁₁— —CH₂-2-naphthyl -5-Tet 334 CH₃NH(CH₂)₁₀— —H —CO₂H 335 CH₃NH(CH₂)₁₀— —CH₃ —CO₂H 336 CH₃NH(CH₂)₁₀— —CH₂CH₃ —CO₂H 337 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₃ —CO₂H 338 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₃ —CO₂H 339 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 340 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 341 CH₃NH(CH₂)₁₀— —CH(CH₃)₂ —CO₂H 342 CH₃NH(CH₂)₁₀— —CH₂CH(CH₃)₂ —CO₂H 343 CH₃NH(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ —CO₂H 344 CH₃NH(CH₂)₁₀— -cyclo-C₃H₅ —CO₂H 345 CH₃NH(CH₂)₁₀— -cyclo-C₄H₇ —CO₂H 346 CH₃NH(CH₂)₁₀— -cyclo-C₅H₉ —CO₂H 347 CH₃NH(CH₂)₁₀— -cyclo-C₆H₁₁ —CO₂H 348 CH₃NH(CH₂)₁₀— -cyclo-C₇H₁₃ —CO₂H 349 CH₃NH(CH₂)₁₀— -cyclo-C₈H₁₅ —CO₂H 350 CH₃NH(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) —CO₂H 351 CH₃NH(CH₂)₁₀— —CH(CH₂CH₃)₂ —CO₂H 352 CH₃NH(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 353 CH₃NH(CH₂)₁₀— —C(CH₃)₃ —CO₂H 354 CH₃NH(CH₂)₁₀— HC≡CCH₂— —CO₂H 355 CH₃NH(CH₂)₁₀— H₂C═CH— —CO₂H 356 CH₃NH(CH₂)₁₀— H₂C═CHCH₂— —CO₂H 357 CH₃NH(CH₂)₁₀— —CH₂F —CO₂H 358 CH₃NH(CH₂)₁₀— —CH₂C₆H₅ —CO₂H 359 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ —CO₂H 360 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ —CO₂H 361 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-F —CO₂H 362 CH₃NH(CH₂)₁₀— —CH₂CH₂C₆H₅ —CO₂H 363 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ —CO₂H 364 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 365 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 366 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 367 CH₃NH(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 368 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₅H₉ —CO₂H 369 CH₃NH(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 370 CH₃NH(CH₂)₁₀— —CH₂-2-naphthyl —CO₂H 371 CH₃NH(CH₂)₁₀— —H —PO₃H₂ 372 CH₃NH(CH₂)₁₀— —CH₃ —PO₃H₂ 373 CH₃NH(CH₂)₁₀— —CH₂CH₃ —PO₃H₂ 374 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₃ —PO₃H₂ 375 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₃ —PO₃H₂ 376 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 377 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 378 CH₃NH(CH₂)₁₀— —CH(CH₃)₂ —PO₃H₂ 379 CH₃NH(CH₂)₁₀— —CH₂CH(CH₃)₂ —PO₃H₂ 380 CH₃NH(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 381 CH₃NH(CH₂)₁₀— -cyclo-C₃H₅ —PO₃H₂ 382 CH₃NH(CH₂)₁₀— -cyclo-C₄H₇ —PO₃H₂ 383 CH₃NH(CH₂)₁₀— -cyclo-C₅H₉ —PO₃H₂ 384 CH₃NH(CH₂)₁₀— -cyclo-C₆H₁₁ —PO₃H₂ 385 CH₃NH(CH₂)₁₀— -cyclo-C₇H₁₃ —PO₃H₂ 386 CH₃NH(CH₂)₁₀— -cyclo-C₈H₁₅ —PO₃H₂ 387 CH₃NH(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 388 CH₃NH(CH₂)₁₀— —CH(CH₂CH₃)₂ —PO₃H₂ 389 CH₃NH(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 390 CH₃NH(CH₂)₁₀— —C(CH₃)₃ —PO₃H₂ 391 CH₃NH(CH₂)₁₀— HC≡CCH₂— —PO₃H₂ 392 CH₃NH(CH₂)₁₀— H₂C═CH— —PO₃H₂ 393 CH₃NH(CH₂)₁₀— H₂C═CHCH₂— —PO₃H₂ 394 CH₃NH(CH₂)₁₀— —CH₂F —PO₃H₂ 395 CH₃NH(CH₂)₁₀— —CH₂C₆H₅ —PO₃H₂ 396 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 397 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 398 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-F —PO₃H₂ 399 CH₃NH(CH₂)₁₀— —CH₂CH₂C₆H₅ —PO₃H₂ 400 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 401 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 402 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 403 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 404 CH₃NH(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 405 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₅H₉ —PO₃H₂ 406 CH₃NH(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 407 CH₃NH(CH₂)₁₀— —CH₂-2-naphthyl —PO₃H₂ 408 CH₃NH(CH₂)₁₀— —H -5-Tet 409 CH₃NH(CH₂)₁₀— —CH₃ -5-Tet 410 CH₃NH(CH₂)₁₀— —CH₂CH₃ -5-Tet 411 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₃ -5-Tet 412 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₃ -5-Tet 413 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 414 CH₃NH(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 415 CH₃NH(CH₂)₁₀— —CH(CH₃)₂ -5-Tet 416 CH₃NH(CH₂)₁₀— —CH₂CH(CH₃)₂ -5-Tet 417 CH₃NH(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ -5-Tet 418 CH₃NH(CH₂)₁₀— -cyclo-C₃H₅ -5-Tet 419 CH₃NH(CH₂)₁₀— -cyclo-C₄H₇ -5-Tet 420 CH₃NH(CH₂)₁₀— -cyclo-C₅H₉ -5-Tet 421 CH₃NH(CH₂)₁₀— -cyclo-C₆H₁₁ -5-Tet 422 CH₃NH(CH₂)₁₀— -cyclo-C₇H₁₃ -5-Tet 423 CH₃NH(CH₂)₁₀— -cyclo-C₈H₁₅ -5-Tet 424 CH₃NH(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) -5-Tet 425 CH₃NH(CH₂)₁₀— —CH(CH₂CH₃)₂ -5-Tet 426 CH₃NH(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 427 CH₃NH(CH₂)₁₀— —C(CH₃)₃ -5-Tet 428 CH₃NH(CH₂)₁₀— HC≡CCH₂— -5-Tet 429 CH₃NH(CH₂)₁₀— H₂C═CH— -5-Tet 430 CH₃NH(CH₂)₁₀— H₂C═CHCH₂— -5-Tet 431 CH₃NH(CH₂)₁₀— —CH₂F -5-Tet 432 CH₃NH(CH₂)₁₀— —CH₂C₆H₅ -5-Tet 433 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ -5-Tet 434 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ -5-Tet 435 CH₃NH(CH₂)₁₀— —CH₂C₆H₄-p-F -5-Tet 436 CH₃NH(CH₂)₁₀— —CH₂CH₂C₆H₅ -5-Tet 437 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ -5-Tet 438 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 439 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 440 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 441 CH₃NH(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 442 CH₃NH(CH₂)₁₀— —CH₂-cyclo-C₅H₉ -5-Tet 443 CH₃NH(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 444 CH₃NH(CH₂)₁₀— —CH₂-2-naphthyl -5-Tet 445 (CH₃)₂N(CH₂)₁₀— —H —CO₂H 446 (CH₃)₂N(CH₂)₁₀— —CH₃ —CO₂H 447 (CH₃)₂N(CH₂)₁₀— —CH₂CH₃ —CO₂H 448 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₃ —CO₂H 449 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₃ —CO₂H 450 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 451 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 452 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)₂ —CO₂H 453 (CH₃)₂N(CH₂)₁₀— —CH₂CH(CH₃)₂ —CO₂H 454 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ —CO₂H 455 (CH₃)₂N(CH₂)₁₀— -cyclo-C₃H₅ —CO₂H 456 (CH₃)₂N(CH₂)₁₀— -cyclo-C₄H₇ —CO₂H 457 (CH₃)₂N(CH₂)₁₀— -cyclo-C₅H₉ —CO₂H 458 (CH₃)₂N(CH₂)₁₀— -cyclo-C₆H₁₁ —CO₂H 459 (CH₃)₂N(CH₂)₁₀— -cyclo-C₇H₁₃ —CO₂H 460 (CH₃)₂N(CH₂)₁₀— -cyclo-C₈H₁₅ —CO₂H 461 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) —CO₂H 462 (CH₃)₂N(CH₂)₁₀— —CH(CH₂CH₃)₂ —CO₂H 463 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 464 (CH₃)₂N(CH₂)₁₀— —C(CH₃)₃ —CO₂H 465 (CH₃)₂N(CH₂)₁₀— HC≡CCH₂— —CO₂H 466 (CH₃)₂N(CH₂)₁₀— H₂C═CH— —CO₂H 467 (CH₃)₂N(CH₂)₁₀— H₂C═CHCH₂— —CO₂H 468 (CH₃)₂N(CH₂)₁₀— —CH₂F —CO₂H 469 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₅ —CO₂H 470 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ —CO₂H 471 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ —CO₂H 472 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-F —CO₂H 473 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂C₆H₅ —CO₂H 474 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ —CO₂H 475 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 476 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 477 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 478 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 479 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₅H₉ —CO₂H 480 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 481 (CH₃)₂N(CH₂)₁₀— —CH₂-2-naphthyl —CO₂H 482 (CH₃)₂N(CH₂)₁₀— —H —PO₃H₂ 483 (CH₃)₂N(CH₂)₁₀— —CH₃ —PO₃H₂ 484 (CH₃)₂N(CH₂)₁₀— —CH₂CH₃ —PO₃H₂ 485 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₃ —PO₃H₂ 486 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₃ —PO₃H₂ 487 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 488 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 489 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)₂ —PO₃H₂ 490 (CH₃)₂N(CH₂)₁₀— —CH₂CH(CH₃)₂ —PO₃H₂ 491 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 492 (CH₃)₂N(CH₂)₁₀— -cyclo-C₃H₅ —PO₃H₂ 493 (CH₃)₂N(CH₂)₁₀— -cyclo-C₄H₇ —PO₃H₂ 494 (CH₃)₂N(CH₂)₁₀— -cyclo-C₅H₉ —PO₃H₂ 495 (CH₃)₂N(CH₂)₁₀— -cyclo-C₆H₁₁ —PO₃H₂ 496 (CH₃)₂N(CH₂)₁₀— -cyclo-C₇H₁₃ —PO₃H₂ 497 (CH₃)₂N(CH₂)₁₀— -cyclo-C₈H₁₅ —PO₃H₂ 498 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 499 (CH₃)₂N(CH₂)₁₀— —CH(CH₂CH₃)₂ —PO₃H₂ 500 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 501 (CH₃)₂N(CH₂)₁₀— —C(CH₃)₃ —PO₃H₂ 502 (CH₃)₂N(CH₂)₁₀— HC≡CCH₂— —PO₃H₂ 503 (CH₃)₂N(CH₂)₁₀— H₂C═CH— —PO₃H₂ 504 (CH₃)₂N(CH₂)₁₀— H₂C═CHCH₂— —PO₃H₂ 505 (CH₃)₂N(CH₂)₁₀— —CH₂F —PO₃H₂ 506 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₅ —PO₃H₂ 507 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 508 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 509 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-F —PO₃H₂ 510 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂C₆H₅ —PO₃H₂ 511 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 512 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 513 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 514 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 515 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 516 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₅H₉ —PO₃H₂ 517 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 518 (CH₃)₂N(CH₂)₁₀— —CH₂-2-naphthyl —PO₃H₂ 519 (CH₃)₂N(CH₂)₁₀— —H -5-Tet 520 (CH₃)₂N(CH₂)₁₀— —CH₃ -5-Tet 521 (CH₃)₂N(CH₂)₁₀— —CH₂CH₃ -5-Tet 522 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₃ -5-Tet 523 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₃ -5-Tet 524 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 525 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 526 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)₂ -5-Tet 527 (CH₃)₂N(CH₂)₁₀— —CH₂CH(CH₃)₂ -5-Tet 528 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂CH(CH₃)₂ -5-Tet 529 (CH₃)₂N(CH₂)₁₀— -cyclo-C₃H₅ -5-Tet 530 (CH₃)₂N(CH₂)₁₀— -cyclo-C₄H₇ -5-Tet 531 (CH₃)₂N(CH₂)₁₀— -cyclo-C₅H₉ -5-Tet 532 (CH₃)₂N(CH₂)₁₀— -cyclo-C₆H₁₁ -5-Tet 533 (CH₃)₂N(CH₂)₁₀— -cyclo-C₇H₁₃ -5-Tet 534 (CH₃)₂N(CH₂)₁₀— -cyclo-C₈H₁₅ -5-Tet 535 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₃) -5-Tet 536 (CH₃)₂N(CH₂)₁₀— —CH(CH₂CH₃)₂ -5-Tet 537 (CH₃)₂N(CH₂)₁₀— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 538 (CH₃)₂N(CH₂)₁₀— —C(CH₃)₃ -5-Tet 539 (CH₃)₂N(CH₂)₁₀— HC≡CCH₂— -5-Tet 540 (CH₃)₂N(CH₂)₁₀— H₂C═CH— -5-Tet 541 (CH₃)₂N(CH₂)₁₀— H₂C═CHCH₂— -5-Tet 542 (CH₃)₂N(CH₂)₁₀— —CH₂F -5-Tet 543 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₅ -5-Tet 544 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-OCH₃ -5-Tet 545 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-CH₃ -5-Tet 546 (CH₃)₂N(CH₂)₁₀— —CH₂C₆H₄-p-F -5-Tet 547 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂C₆H₅ -5-Tet 548 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₁ -5-Tet 549 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 550 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 551 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 552 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 553 (CH₃)₂N(CH₂)₁₀— —CH₂-cyclo-C₅H₉ -5-Tet 554 (CH₃)₂N(CH₂)₁₀— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 555 (CH₃)₂N(CH₂)₁₀— —CH₂-2-naphthyl -5-Tet 556 p-[H₂N(CH₂)₆]C₆H₄CH₂— —H —CO₂H 557 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₃ —CO₂H 558 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₃ —CO₂H 559 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₃ —CO₂H 560 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —CO₂H 561 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 562 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 563 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)₂ —CO₂H 564 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH(CH₃)₂ —CO₂H 565 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —CO₂H 566 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₃H₅ —CO₂H 567 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₄H₇ —CO₂H 568 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₅H₉ —CO₂H 569 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₆H₁₁ —CO₂H 570 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₇H₁₃ —CO₂H 571 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₈H₁₅ —CO₂H 572 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —CO₂H 573 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₂CH₃)₂ —CO₂H 574 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 575 p-[H₂N(CH₂)₆]C₆H₄CH₂— —C(CH₃)₃ —CO₂H 576 p-[H₂N(CH₂)₆]C₆H₄CH₂— HC≡CCH₂— —CO₂H 577 p-[H₂N(CH₂)₆]C₆H₄CH₂— H₂C═CH— —CO₂H 578 p-[H₂N(CH₂)₆]C₆H₄CH₂— H₂C═CHCH₂— —CO₂H 579 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂F —CO₂H 580 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₅ —CO₂H 581 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —CO₂H 582 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —CO₂H 583 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-F —CO₂H 584 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂C₆H₅ —CO₂H 585 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —CO₂H 586 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 587 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 588 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 589 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 590 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —CO₂H 591 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 592 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-2-naphthyl —CO₂H 593 p-[H₂N(CH₂)₆]C₆H₄CH₂— —H —PO₃H₂ 594 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₃ —PO₃H₂ 595 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₃ —PO₃H₂ 596 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₃ —PO₃H₂ 597 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —PO₃H₂ 598 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 599 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 600 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)₂ —PO₃H₂ 601 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH(CH₃)₂ —PO₃H₂ 602 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 603 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₃H₅ —PO₃H₂ 604 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₄H₇ —PO₃H₂ 605 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₅H₉ —PO₃H₂ 606 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₆H₁₁ —PO₃H₂ 607 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₇H₁₃ —PO₃H₂ 608 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₈H₁₅ —PO₃H₂ 609 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 610 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₂CH₃)₂ —PO₃H₂ 611 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 612 p-[H₂N(CH₂)₆]C₆H₄CH₂— —C(CH₃)₃ —PO₃H₂ 613 p-[H₂N(CH₂)₆]C₆H₄CH₂— HC≡CCH₂— —PO₃H₂ 614 p-[H₂N(CH₂)₆]C₆H₄CH₂— H₂C═CH— —PO₃H₂ 615 p-[H₂N(CH₂)₆]C₆H₄CH₂— H₂C═CHCH₂— —PO₃H₂ 616 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂F —PO₃H₂ 617 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₅ —PO₃H₂ 618 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 619 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 620 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-F —PO₃H₂ 621 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂C₆H₅ —PO₃H₂ 622 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 623 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 624 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 625 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 626 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 627 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —PO₃H₂ 628 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 629 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-2-naphthyl —PO₃H₂ 630 p-[H₂N(CH₂)₆]C₆H₄CH₂— —H -5-Tet 631 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₃ -5-Tet 632 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₃ -5-Tet 633 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₃ -5-Tet 634 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ -5-Tet 635 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 636 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 637 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)₂ -5-Tet 638 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH(CH₃)₂ -5-Tet 639 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ -5-Tet 640 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₃H₅ -5-Tet 641 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₄H₇ -5-Tet 642 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₅H₉ -5-Tet 643 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₆H₁₁ -5-Tet 644 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₇H₁₃ -5-Tet 645 p-[H₂N(CH₂)₆]C₆H₄CH₂— -cyclo-C₈H₁₅ -5-Tet 646 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) -5-Tet 647 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₂CH₃)₂ -5-Tet 648 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 649 p-[H₂N(CH₂)₆]C₆H₄CH₂— —C(CH₃)₃ -5-Tet 650 p-[H₂N(CH₂)₆]C₆H₄CH₂— HC≡CCH₂— -5-Tet 651 p-[H₂N(CH₂)₆]C₆H₄CH₂— H₂C═CH— -5-Tet 652 p-[H₂N(CH₂)₆]C₆H₄CH₂— H₂C═CHCH₂— -5-Tet 653 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂F -5-Tet 654 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₅ -5-Tet 655 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ -5-Tet 656 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ -5-Tet 657 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂C₆H₄-p-F -5-Tet 658 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂C₆H₅ -5-Tet 659 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ -5-Tet 660 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 661 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 662 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 663 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 664 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ -5-Tet 665 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 666 p-[H₂N(CH₂)₆]C₆H₄CH₂— —CH₂-2-naphthyl -5-Tet 667 p-[H₂N(CH₂)₈]C₆H₄CH₂— —H —CO₂H 668 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₃ —CO₂H 669 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₃ —CO₂H 670 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₃ —CO₂H 671 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —CO₂H 672 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 673 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 674 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)₂ —CO₂H 675 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH(CH₃)₂ —CO₂H 676 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —CO₂H 677 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₃H₅ —CO₂H 678 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₄H₇ —CO₂H 679 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₅H₉ —CO₂H 680 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₆H₁₁ —CO₂H 681 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₇H₁₃ —CO₂H 682 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₈H₁₅ —CO₂H 683 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —CO₂H 684 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₂CH₃)₂ —CO₂H 685 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 686 p-[H₂N(CH₂)₈]C₆H₄CH₂— —C(CH₃)₃ —CO₂H 687 p-[H₂N(CH₂)₈]C₆H₄CH₂— HC≡CCH₂— —CO₂H 688 p-[H₂N(CH₂)₈]C₆H₄CH₂— H₂C═CH— —CO₂H 689 p-[H₂N(CH₂)₈]C₆H₄CH₂— H₂C═CHCH₂— —CO₂H 690 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂F —CO₂H 691 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₅ —CO₂H 692 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —CO₂H 693 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —CO₂H 694 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-F —CO₂H 695 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂C₆H₅ —CO₂H 696 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —CO₂H 697 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 698 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 699 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 700 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 701 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —CO₂H 702 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 703 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-2-naphthyl —CO₂H 704 p-[H₂N(CH₂)₈]C₆H₄CH₂— —H —PO₃H₂ 705 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₃ —PO₃H₂ 706 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₃ —PO₃H₂ 707 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₃ —PO₃H₂ 708 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —PO₃H₂ 709 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 710 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 711 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)₂ —PO₃H₂ 712 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH(CH₃)₂ —PO₃H₂ 713 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 714 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₃H₅ —PO₃H₂ 715 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₄H₇ —PO₃H₂ 716 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₅H₉ —PO₃H₂ 717 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₆H₁₁ —PO₃H₂ 718 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₇H₁₃ —PO₃H₂ 719 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₈H₁₅ —PO₃H₂ 720 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 721 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₂CH₃)₂ —PO₃H₂ 722 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 723 p-[H₂N(CH₂)₈]C₆H₄CH₂— —C(CH₃)₃ —PO₃H₂ 724 p-[H₂N(CH₂)₈]C₆H₄CH₂— HC≡CCH₂— —PO₃H₂ 725 p-[H₂N(CH₂)₈]C₆H₄CH₂— H₂C═CH— —PO₃H₂ 726 p-[H₂N(CH₂)₈]C₆H₄CH₂— H₂C═CHCH₂— —PO₃H₂ 727 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂F —PO₃H₂ 728 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₅ —PO₃H₂ 729 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 730 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 731 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-F —PO₃H₂ 732 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂C₆H₅ —PO₃H₂ 733 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 734 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 735 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 736 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 737 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 738 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —PO₃H₂ 739 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 740 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-2-naphthyl —PO₃H₂ 741 p-[H₂N(CH₂)₈]C₆H₄CH₂— —H -5-Tet 742 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₃ -5-Tet 743 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₃ -5-Tet 744 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₃ -5-Tet 745 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ -5-Tet 746 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 747 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 748 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)₂ -5-Tet 749 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH(CH₃)₂ -5-Tet 750 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ -5-Tet 751 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₃H₅ -5-Tet 752 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₄H₇ -5-Tet 753 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₅H₉ -5-Tet 754 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₆H₁₁ -5-Tet 755 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₇H₁₃ -5-Tet 756 p-[H₂N(CH₂)₈]C₆H₄CH₂— -cyclo-C₈H₁₅ -5-Tet 757 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) -5-Tet 758 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₂CH₃)₂ -5-Tet 759 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 760 p-[H₂N(CH₂)₈]C₆H₄CH₂— —C(CH₃)₃ -5-Tet 761 p-[H₂N(CH₂)₈]C₆H₄CH₂— HC≡CCH₂— -5-Tet 762 p-[H₂N(CH₂)₈]C₆H₄CH₂— H₂C═CH— -5-Tet 763 p-[H₂N(CH₂)₈]C₆H₄CH₂— H₂C═CHCH₂— -5-Tet 764 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂F -5-Tet 765 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₅ -5-Tet 766 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ -5-Tet 767 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ -5-Tet 768 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂C₆H₄-p-F -5-Tet 769 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂C₆H₅ -5-Tet 770 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ -5-Tet 771 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 772 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 773 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 774 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 775 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ -5-Tet 776 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 777 p-[H₂N(CH₂)₈]C₆H₄CH₂— —CH₂-2-naphthyl -5-Tet 778 p-[H₂N(CH₂)₉]C₆H₄CH₂— —H —CO₂H 779 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₃ —CO₂H 780 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₃ —CO₂H 781 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₃ —CO₂H 782 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —CO₂H 783 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 784 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 785 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)₂ —CO₂H 786 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH(CH₃)₂ —CO₂H 787 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —CO₂H 788 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₃H₅ —CO₂H 789 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₄H₇ —CO₂H 790 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₅H₉ —CO₂H 791 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₆H₁₁ —CO₂H 792 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₇H₁₃ —CO₂H 793 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₈H₁₅ —CO₂H 794 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —CO₂H 795 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₂CH₃)₂ —CO₂H 796 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 797 p-[H₂N(CH₂)₉]C₆H₄CH₂— —C(CH₃)₃ —CO₂H 798 p-[H₂N(CH₂)₉]C₆H₄CH₂— HC≡CCH₂— —CO₂H 799 p-[H₂N(CH₂)₉]C₆H₄CH₂— H₂C═CH— —CO₂H 800 p-[H₂N(CH₂)₉]C₆H₄CH₂— H₂C═CHCH₂— —CO₂H 801 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂F —CO₂H 802 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₅ —CO₂H 803 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —CO₂H 804 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —CO₂H 805 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-F —CO₂H 806 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂C₆H₅ —CO₂H 807 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —CO₂H 808 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 809 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 810 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 811 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 812 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —CO₂H 813 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 814 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-2-naphthyl —CO₂H 815 p-[H₂N(CH₂)₉]C₆H₄CH₂— —H —PO₃H₂ 816 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₃ —PO₃H₂ 817 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₃ —PO₃H₂ 818 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₃ —PO₃H₂ 819 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —PO₃H₂ 820 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 821 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 822 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)₂ —PO₃H₂ 823 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH(CH₃)₂ —PO₃H₂ 824 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 825 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₃H₅ —PO₃H₂ 826 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₄H₇ —PO₃H₂ 827 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₅H₉ —PO₃H₂ 828 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₆H₁₁ —PO₃H₂ 829 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₇H₁₃ —PO₃H₂ 830 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₈H₁₅ —PO₃H₂ 831 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 832 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₂CH₃)₂ —PO₃H₂ 833 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 834 p-[H₂N(CH₂)₉]C₆H₄CH₂— —C(CH₃)₃ —PO₃H₂ 835 p-[H₂N(CH₂)₉]C₆H₄CH₂— HC≡CCH₂— —PO₃H₂ 836 p-[H₂N(CH₂)₉]C₆H₄CH₂— H₂C═CH— —PO₃H₂ 837 p-[H₂N(CH₂)₉]C₆H₄CH₂— H₂C═CHCH₂— —PO₃H₂ 838 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂F —PO₃H₂ 839 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₅ —PO₃H₂ 840 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 841 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 842 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-F —PO₃H₂ 843 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂C₆H₅ —PO₃H₂ 844 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 845 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 846 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 847 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 848 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 849 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —PO₃H₂ 850 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 851 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-2-naphthyl —PO₃H₂ 852 p-[H₂N(CH₂)₉]C₆H₄CH₂— —H -5-Tet 853 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₃ -5-Tet 854 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₃ -5-Tet 855 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₃ -5-Tet 856 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ -5-Tet 857 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 858 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 859 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)₂ -5-Tet 860 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH(CH₃)₂ -5-Tet 861 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ -5-Tet 862 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₃H₅ -5-Tet 863 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₄H₇ -5-Tet 864 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₅H₉ -5-Tet 865 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₆H₁₁ -5-Tet 866 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₇H₁₃ -5-Tet 867 p-[H₂N(CH₂)₉]C₆H₄CH₂— -cyclo-C₈H₁₅ -5-Tet 868 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) -5-Tet 869 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₂CH₃)₂ -5-Tet 870 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 871 p-[H₂N(CH₂)₉]C₆H₄CH₂— —C(CH₃)₃ -5-Tet 872 p-[H₂N(CH₂)₉]C₆H₄CH₂— HC≡CCH₂— -5-Tet 873 p-[H₂N(CH₂)₉]C₆H₄CH₂— H₂C═CH— -5-Tet 874 p-[H₂N(CH₂)₉]C₆H₄CH₂— H₂C═CHCH₂— -5-Tet 875 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂F -5-Tet 876 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₅ -5-Tet 877 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ -5-Tet 878 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ -5-Tet 879 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂C₆H₄-p-F -5-Tet 880 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂C₆H₅ -5-Tet 881 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ -5-Tet 882 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 883 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 884 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 885 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 886 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ -5-Tet 887 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 888 p-[H₂N(CH₂)₉]C₆H₄CH₂— —CH₂-2-naphthyl -5-Tet 889 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —H —CO₂H 890 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₃ —CO₂H 891 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₃ —CO₂H 892 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₃ —CO₂H 893 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —CO₂H 894 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 895 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 896 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)₂ —CO₂H 897 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH(CH₃)₂ —CO₂H 898 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —CO₂H 899 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₃H₅ —CO₂H 900 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₄H₇ —CO₂H 901 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₅H₉ —CO₂H 902 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₆H₁₁ —CO₂H 903 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₇H₁₃ —CO₂H 904 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₈H₁₅ —CO₂H 905 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —CO₂H 906 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₂CH₃)₂ —CO₂H 907 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 908 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —C(CH₃)₃ —CO₂H 909 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— HC≡CCH₂— —CO₂H 910 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— H₂C═CH— —CO₂H 911 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— H₂C═CHCH₂— —CO₂H 912 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂F —CO₂H 913 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₅ —CO₂H 914 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —CO₂H 915 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —CO₂H 916 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-F —CO₂H 917 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂C₆H₅ —CO₂H 918 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —CO₂H 919 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 920 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 921 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 922 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 923 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —CO₂H 924 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 925 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-2-naphthyl —CO₂H 926 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —H —PO₃H₂ 927 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₃ —PO₃H₂ 928 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₃ —PO₃H₂ 929 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₃ —PO₃H₂ 930 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ —PO₃H₂ 931 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 932 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 933 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)₂ —PO₃H₂ 934 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH(CH₃)₂ —PO₃H₂ 935 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 936 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₃H₅ —PO₃H₂ 937 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₄H₇ —PO₃H₂ 938 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₅H₉ —PO₃H₂ 939 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₆H₁₁ —PO₃H₂ 940 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₇H₁₃ —PO₃H₂ 941 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₈H₁₅ —PO₃H₂ 942 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 943 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₂CH₃)₂ —PO₃H₂ 944 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 945 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —C(CH₃)₃ —PO₃H₂ 946 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— HC≡CCH₂— —PO₃H₂ 947 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— H₂C═CH— —PO₃H₂ 948 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— H₂C═CHCH₂— —PO₃H₂ 949 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂F —PO₃H₂ 950 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₅ —PO₃H₂ 951 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 952 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 953 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-F —PO₃H₂ 954 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂C₆H₅ —PO₃H₂ 955 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 956 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 957 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 958 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 959 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 960 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ —PO₃H₂ 961 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 962 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-2-naphthyl —PO₃H₂ 963 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —H -5-Tet 964 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₃ -5-Tet 965 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₃ -5-Tet 966 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₃ -5-Tet 967 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₃ -5-Tet 968 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 969 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 970 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)₂ -5-Tet 971 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH(CH₃)₂ -5-Tet 972 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂CH(CH₃)₂ -5-Tet 973 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₃H₅ -5-Tet 974 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₄H₇ -5-Tet 975 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₅H₉ -5-Tet 976 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₆H₁₁ -5-Tet 977 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₇H₁₃ -5-Tet 978 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— -cyclo-C₈H₁₅ -5-Tet 979 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)(CH₂CH₃) -5-Tet 980 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₂CH₃)₂ -5-Tet 981 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 982 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —C(CH₃)₃ -5-Tet 983 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— HC≡CCH₂— -5-Tet 984 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— H₂C═CH— -5-Tet 985 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— H₂C═CHCH₂— -5-Tet 986 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂F -5-Tet 987 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₅ -5-Tet 988 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-OCH₃ -5-Tet 989 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-CH₃ -5-Tet 990 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂C₆H₄-p-F -5-Tet 991 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂C₆H₅ -5-Tet 992 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₁ -5-Tet 993 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 994 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 995 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 996 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 997 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-cyclo-C₅H₉ -5-Tet 998 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 999 p-[H₂N(CH₂)₁₀]C₆H₄CH₂— —CH₂-2-naphthyl -5-Tet 1000 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —H —CO₂H 1001 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₃ —CO₂H 1002 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₃ —CO₂H 1003 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —CO₂H 1004 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —CO₂H 1005 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 1006 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1007 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)₂ —CO₂H 1008 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —CO₂H 1009 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —CO₂H 1010 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —CO₂H 1011 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —CO₂H 1012 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —CO₂H 1013 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —CO₂H 1014 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —CO₂H 1015 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —CO₂H 1016 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —CO₂H 1017 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —CO₂H 1018 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1019 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —C(CH₃)₃ —CO₂H 1020 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— HC≡CCH₂— —CO₂H 1021 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— H₂C═CH— —CO₂H 1022 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— H₂C═CHCH₂— —CO₂H 1023 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂F —CO₂H 1024 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₅ —CO₂H 1025 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —CO₂H 1026 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —CO₂H 1027 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —CO₂H 1028 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —CO₂H 1029 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —CO₂H 1030 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1031 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1032 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1033 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1034 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —CO₂H 1035 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 1036 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —CO₂H 1037 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —H —PO₃H₂ 1038 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₃ —PO₃H₂ 1039 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₃ —PO₃H₂ 1040 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —PO₃H₂ 1041 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —PO₃H₂ 1042 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1043 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1044 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)₂ —PO₃H₂ 1045 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —PO₃H₂ 1046 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1047 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —PO₃H₂ 1048 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —PO₃H₂ 1049 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —PO₃H₂ 1050 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —PO₃H₂ 1051 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —PO₃H₂ 1052 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —PO₃H₂ 1053 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 1054 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —PO₃H₂ 1055 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1056 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —C(CH₃)₃ —PO₃H₂ 1057 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— HC≡CCH₂— —PO₃H₂ 1058 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— H₂C═CH— —PO₃H₂ 1059 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— H₂C═CHCH₂— —PO₃H₂ 1060 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂F —PO₃H₂ 1061 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₅ —PO₃H₂ 1062 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1063 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 1064 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —PO₃H₂ 1065 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —PO₃H₂ 1066 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1067 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1068 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1069 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1070 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1071 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —PO₃H₂ 1072 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1073 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —PO₃H₂ 1074 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —H -5-Tet 1075 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₃ -5-Tet 1076 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₃ -5-Tet 1077 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ -5-Tet 1078 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ -5-Tet 1079 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 1080 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1081 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)₂ -5-Tet 1082 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ -5-Tet 1083 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ -5-Tet 1084 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₃H₅ -5-Tet 1085 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₄H₇ -5-Tet 1086 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₅H₉ -5-Tet 1087 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ -5-Tet 1088 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ -5-Tet 1089 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ -5-Tet 1090 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) -5-Tet 1091 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ -5-Tet 1092 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1093 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —C(CH₃)₃ -5-Tet 1094 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— HC≡CCH₂— -5-Tet 1095 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— H₂C═CH— -5-Tet 1096 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— H₂C═CHCH₂— -5-Tet 1097 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂F -5-Tet 1098 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₅ -5-Tet 1099 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ -5-Tet 1100 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ -5-Tet 1101 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F -5-Tet 1102 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ -5-Tet 1103 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ -5-Tet 1104 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1105 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1106 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1107 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1108 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ -5-Tet 1109 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 1110 p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)— —CH₂-2-naphthyl -5-Tet 1111 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —H —CO₂H 1112 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₃ —CO₂H 1113 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₃ —CO₂H 1114 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —CO₂H 1115 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —CO₂H 1116 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 1117 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1118 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)₂ —CO₂H 1119 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —CO₂H 1120 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —CO₂H 1121 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —CO₂H 1122 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —CO₂H 1123 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —CO₂H 1124 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —CO₂H 1125 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —CO₂H 1126 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —CO₂H 1127 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —CO₂H 1128 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —CO₂H 1129 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1130 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —C(CH₃)₃ —CO₂H 1131 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— HC≡CCH₂— —CO₂H 1132 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— H₂C═CH— —CO₂H 1133 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— H₂C═CHCH₂— —CO₂H 1134 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂F —CO₂H 1135 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₅ —CO₂H 1136 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —CO₂H 1137 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —CO₂H 1138 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —CO₂H 1139 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —CO₂H 1140 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —CO₂H 1141 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1142 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1143 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1144 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1145 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —CO₂H 1146 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 1147 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —CO₂H 1148 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —H —PO₃H₂ 1149 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₃ —PO₃H₂ 1150 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₃ —PO₃H₂ 1151 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —PO₃H₂ 1152 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —PO₃H₂ 1153 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1154 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1155 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)₂ —PO₃H₂ 1156 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —PO₃H₂ 1157 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1158 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —PO₃H₂ 1159 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —PO₃H₂ 1160 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —PO₃H₂ 1161 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —PO₃H₂ 1162 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —PO₃H₂ 1163 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —PO₃H₂ 1164 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 1165 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —PO₃H₂ 1166 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1167 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —C(CH₃)₃ —PO₃H₂ 1168 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— HC≡CCH₂— —PO₃H₂ 1169 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— H₂C═CH— —PO₃H₂ 1170 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— H₂C═CHCH₂— —PO₃H₂ 1171 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂F —PO₃H₂ 1172 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₅ —PO₃H₂ 1173 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1174 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 1175 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —PO₃H₂ 1176 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —PO₃H₂ 1177 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1178 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1179 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1180 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1181 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1182 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —PO₃H₂ 1183 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1184 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —PO₃H₂ 1185 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —H -5-Tet 1186 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₃ -5-Tet 1187 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₃ -5-Tet 1188 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ -5-Tet 1189 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ -5-Tet 1190 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 1191 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1192 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)₂ -5-Tet 1193 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ -5-Tet 1194 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ -5-Tet 1195 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₃H₅ -5-Tet 1196 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₄H₇ -5-Tet 1197 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₅H₉ -5-Tet 1198 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ -5-Tet 1199 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ -5-Tet 1200 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ -5-Tet 1201 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) -5-Tet 1202 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ -5-Tet 1203 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1204 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —C(CH₃)₃ -5-Tet 1205 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— HC≡CCH₂— -5-Tet 1206 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— H₂C═CH— -5-Tet 1207 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— H₂C═CHCH₂— -5-Tet 1208 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂F -5-Tet 1209 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₅ -5-Tet 1210 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ -5-Tet 1211 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ -5-Tet 1212 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F -5-Tet 1213 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ -5-Tet 1214 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ -5-Tet 1215 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1216 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1217 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1218 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1219 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ -5-Tet 1220 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 1221 p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)— —CH₂-2-naphthyl -5-Tet 1222 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —H —CO₂H 1223 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₃ —CO₂H 1224 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₃ —CO₂H 1225 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —CO₂H 1226 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —CO₂H 1227 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 1228 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1229 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)₂ —CO₂H 1230 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —CO₂H 1231 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —CO₂H 1232 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —CO₂H 1233 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —CO₂H 1234 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —CO₂H 1235 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —CO₂H 1236 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —CO₂H 1237 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —CO₂H 1238 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —CO₂H 1239 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —CO₂H 1240 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1241 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —C(CH₃)₃ —CO₂H 1242 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— HC≡CCH₂— —CO₂H 1243 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— H₂C═CH— —CO₂H 1244 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— H₂C═CHCH₂— —CO₂H 1245 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂F —CO₂H 1246 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₅ —CO₂H 1247 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —CO₂H 1248 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —CO₂H 1249 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —CO₂H 1250 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —CO₂H 1251 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —CO₂H 1252 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1253 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1254 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1255 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1256 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —CO₂H 1257 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 1258 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —CO₂H 1259 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —H —PO₃H₂ 1260 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₃ —PO₃H₂ 1261 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₃ —PO₃H₂ 1262 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —PO₃H₂ 1263 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —PO₃H₂ 1264 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1265 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1266 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)₂ —PO₃H₂ 1267 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —PO₃H₂ 1268 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1269 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —PO₃H₂ 1270 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —PO₃H₂ 1271 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —PO₃H₂ 1272 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —PO₃H₂ 1273 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —PO₃H₂ 1274 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —PO₃H₂ 1275 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 1276 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —PO₃H₂ 1277 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1278 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —C(CH₃)₃ —PO₃H₂ 1279 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— HC≡CCH₂— —PO₃H₂ 1280 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— H₂C═CH— —PO₃H₂ 1281 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— H₂C═CHCH₂— —PO₃H₂ 1282 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂F —PO₃H₂ 1283 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₅ —PO₃H₂ 1284 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1285 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 1286 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —PO₃H₂ 1287 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —PO₃H₂ 1288 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1289 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1290 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1291 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1292 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1293 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —PO₃H₂ 1294 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1295 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —PO₃H₂ 1296 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —H -5-Tet 1297 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₃ -5-Tet 1298 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₃ -5-Tet 1299 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ -5-Tet 1300 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ -5-Tet 1301 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 1302 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1303 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)₂ -5-Tet 1304 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ -5-Tet 1305 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ -5-Tet 1306 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₃H₅ -5-Tet 1307 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₄H₇ -5-Tet 1308 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₅H₉ -5-Tet 1309 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ -5-Tet 1310 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ -5-Tet 1311 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ -5-Tet 1312 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) -5-Tet 1313 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ -5-Tet 1314 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1315 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —C(CH₃)₃ -5-Tet 1316 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— HC≡CCH₂— -5-Tet 1317 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— H₂C═CH— -5-Tet 1318 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— H₂C═CHCH₂— -5-Tet 1319 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂F -5-Tet 1320 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₅ -5-Tet 1321 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ -5-Tet 1322 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ -5-Tet 1323 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F -5-Tet 1324 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ -5-Tet 1325 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ -5-Tet 1326 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1327 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1328 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1329 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1330 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ -5-Tet 1331 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 1332 p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)— —CH₂-2-naphthyl -5-Tet 1333 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —H —CO₂H 1334 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₃ —CO₂H 1335 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH_(3)—) —CH₂CH₃ —CO₂H 1336 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —CO₂H 1337 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —CO₂H 1338 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 1339 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1340 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)₂ —CO₂H 1341 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —CO₂H 1342 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —CO₂H 1343 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —CO₂H 1344 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —CO₂H 1345 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —CO₂H 1346 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —CO₂H 1347 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —CO₂H 1348 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —CO₂H 1349 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —CO₂H 1350 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —CO₂H 1351 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1352 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —C(CH₃)₃ —CO₂H 1353 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— HC≡CCH₂— —CO₂H 1354 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— H₂C═CH— —CO₂H 1355 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— H₂C═CHCH₂— —CO₂H 1356 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂F —CO₂H 1357 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₅ —CO₂H 1358 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —CO₂H 1359 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —CO₂H 1360 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —CO₂H 1361 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —CO₂H 1362 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —CO₂H 1363 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1364 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1365 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1366 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1367 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —CO₂H 1368 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —CO₂H 1369 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —CO₂H 1370 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —H —PO₃H₂ 1371 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₃ —PO₃H₂ 1372 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₃ —PO₃H₂ 1373 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ —PO₃H₂ 1374 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ —PO₃H₂ 1375 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1376 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1377 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)₂ —PO₃H₂ 1378 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ —PO₃H₂ 1379 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1380 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₃H₅ —PO₃H₂ 1381 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₄H₇ —PO₃H₂ 1382 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₅H₉ —PO₃H₂ 1383 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ —PO₃H₂ 1384 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ —PO₃H₂ 1385 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ —PO₃H₂ 1386 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) —PO₃H₂ 1387 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ —PO₃H₂ 1388 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1389 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —C(CH₃)₃ —PO₃H₂ 1390 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— HC≡CCH₂— —PO₃H₂ 1391 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— H₂C═CH— —PO₃H₂ 1392 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— H₂C═CHCH₂— —PO₃H₂ 1393 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂F —PO₃H₂ 1394 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₅ —PO₃H₂ 1395 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1396 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ —PO₃H₂ 1397 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F —PO₃H₂ 1398 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ —PO₃H₂ 1399 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1400 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1401 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1402 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1403 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1404 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ —PO₃H₂ 1405 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1406 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-2-naphthyl —PO₃H₂ 1407 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —H -5-Tet 1408 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₃ -5-Tet 1409 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₃ -5-Tet 1410 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₃ -5-Tet 1411 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₃ -5-Tet 1412 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₃ -5-Tet 1413 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1414 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)₂ -5-Tet 1415 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH(CH₃)₂ -5-Tet 1416 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂CH(CH₃)₂ -5-Tet 1417 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₃H₅ -5-Tet 1418 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₄H₇ -5-Tet 1419 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₅H₉ -5-Tet 1420 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₆H₁₁ -5-Tet 1421 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₇H₁₃ -5-Tet 1422 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— -cyclo-C₈H₁₅ -5-Tet 1423 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₃) -5-Tet 1424 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₂CH₃)₂ -5-Tet 1425 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1426 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —C(CH₃)₃ -5-Tet 1427 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— HC≡CCH₂— -5-Tet 1428 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— H₂C═CH— -5-Tet 1429 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— H₂C═CHCH₂— -5-Tet 1430 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂F -5-Tet 1431 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₅ -5-Tet 1432 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-OCH₃ -5-Tet 1433 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-CH₃ -5-Tet 1434 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂C₆H₄-p-F -5-Tet 1435 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂C₆H₅ -5-Tet 1436 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₁ -5-Tet 1437 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1438 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1439 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1440 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1441 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-cyclo-C₅H₉ -5-Tet 1442 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂CH₂-cyclo-C₅H₉ -5-Tet 1443 p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)— —CH₂-2-naphthyl -5-Tet 1444

—H —CO₂H 1445

—CH₃ —CO₂H 1446

—CH₂CH₃ —CO₂H 1447

—CH₂CH₂CH₃ —CO₂H 1448

—CH₂CH₂CH₂CH₃ —CO₂H 1449

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 1450

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1451

—CH(CH₃)₂ —CO₂H 1452

—CH₂CH(CH₃)₂ —CO₂H 1453

—CH₂CH₂CH(CH₃)₂ —CO₂H 1454

-cyclo-C₃H₅ —CO₂H 1455

-cyclo-C₄H₇ —CO₂H 1456

-cyclo-C₅H₉ —CO₂H 1457

-cyclo-C₆H₁₁ —CO₂H 1458

-cyclo-C₇H₁₃ —CO₂H 1459

-cyclo-C₈H₁₅ —CO₂H 1460

—CH(CH₃)(CH₂CH₃) —CO₂H 1461

—CH(CH₂CH₃)₂ —CO₂H 1462

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1463

—C(CH₃)₃ —CO₂H 1464

HC≡CCH₂— —CO₂H 1465

H₂C═CH— —CO₂H 1466

H₂C═CHCH₂— —CO₂H 1467

—CH₂F —CO₂H 1468

—CH₂C₆H₅ —CO₂H 1469

—CH₂C₆H₄-p-OCH₃ —CO₂H 1470

—CH₂C₆H₄-p-CH₃ —CO₂H 1471

—CH₂C₆H₄-p-F —CO₂H 1472

—CH₂CH₂C₆H₅ —CO₂H 1473

—CH₂-cyclo-C₆H₁₁ —CO₂H 1474

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1475

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1476

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1477

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1478

—CH₂-cyclo-C₅H₉ —CO₂H 1479

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 1480

—CH₂-2-naphthyl —CO₂H 1481

—H —PO₃H₂ 1482

—CH₃ —PO₃H₂ 1483

—CH₂CH₃ —PO₃H₂ 1484

—CH₂CH₂CH₃ —PO₃H₂ 1485

—CH₂CH₂CH₂CH₃ —PO₃H₂ 1486

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1487

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1488

—CH(CH₃)₂ —PO₃H₂ 1489

—CH₂CH(CH₃)₂ —PO₃H₂ 1490

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1491

-cyclo-C₃H₅ —PO₃H₂ 1492

-cyclo-C₄H₇ —PO₃H₂ 1493

-cyclo-C₅H₉ —PO₃H₂ 1494

-cyclo-C₆H₁₁ —PO₃H₂ 1495

-cyclo-C₇H₁₃ —PO₃H₂ 1496

-cyclo-C₈H₁₅ —PO₃H₂ 1497

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 1498

—CH(CH₂CH₃)₂ —PO₃H₂ 1499

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1500

—C(CH₃)₃ —PO₃H₂ 1501

HC≡CCH₂— —PO₃H₂ 1502

H₂C═CH— —PO₃H₂ 1503

H₂C═CHCH₂— —PO₃H₂ 1504

—CH₂F —PO₃H₂ 1505

—CH₂C₆H₅ —PO₃H₂ 1506

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1507

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 1508

—CH₂C₆H₄-p-F —PO₃H₂ 1509

—CH₂CH₂C₆H₅ —PO₃H₂ 1510

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1511

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1512

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1513

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1514

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1515

—CH₂-cyclo-C₅H₉ —PO₃H₂ 1516

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1517

—CH₂-2-naphthyl —PO₃H₂ 1518

—H -5-Tet 1519

—CH₃ -5-Tet 1520

—CH₂CH₃ -5-Tet 1521

—CH₂CH₂CH₃ -5-Tet 1522

—CH₂CH₂CH₂CH₃ -5-Tet 1523

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 1524

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1525

—CH(CH₃)₂ -5-Tet 1526

—CH₂CH(CH₃)₂ -5-Tet 1527

—CH₂CH₂CH(CH₃)₂ -5-Tet 1528

-cyclo-C₃H₅ -5-Tet 1529

-cyclo-C₄H₇ -5-Tet 1530

-cyclo-C₅H₉ -5-Tet 1531

-cyclo-C₆H₁₁ -5-Tet 1532

-cyclo-C₇H₁₃ -5-Tet 1533

-cyclo-C₈H₁₅ -5-Tet 1534

—CH(CH₃)(CH₂CH₃) -5-Tet 1535

—CH(CH₂CH₃)₂ -5-Tet 1536

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1537

—C(CH₃)₃ -5-Tet 1538

HC≡CCH₂— -5-Tet 1539

H₂C═CH— -5-Tet 1540

H₂C═CHCH₂— -5-Tet 1541

—CH₂F -5-Tet 1542

—CH₂C₆H₅ -5-Tet 1543

—CH₂C₆H₄-p-OCH₃ -5-Tet 1544

—CH₂C₆H₄-p-CH₃ -5-Tet 1545

—CH₂C₆H₄-p-F -5-Tet 1546

—CH₂CH₂C₆H₅ -5-Tet 1547

—CH₂-cyclo-C₆H₁₁ -5-Tet 1548

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1549

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1550

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1551

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1552

—CH₂-cyclo-C₅H₉ -5-Tet 1553

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 1554

—CH₂-2-naphthyl -5-Tet 1555

—H —CO₂H 1556

—CH₃ —CO₂H 1557

—CH₂CH₃ —CO₂H 1558

—CH₂CH₂CH₃ —CO₂H 1559

—CH₂CH₂CH₂CH₃ —CO₂H 1560

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 1561

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1562

—CH(CH₃)₂ —CO₂H 1563

—CH₂CH(CH₃)₂ —CO₂H 1564

—CH₂CH₂CH(CH₃)₂ —CO₂H 1565

-cyclo-C₃H₅ —CO₂H 1566

-cyclo-C₄H₇ —CO₂H 1567

-cyclo-C₅H₉ —CO₂H 1568

-cyclo-C₆H₁₁ —CO₂H 1569

-cyclo-C₇H₁₃ —CO₂H 1570

-cyclo-C₈H₁₅ —CO₂H 1571

—CH(CH₃)(CH₂CH₃) —CO₂H 1572

—CH(CH₂CH₃)₂ —CO₂H 1573

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1574

—C(CH₃)₃ —CO₂H 1575

HC≡CCH₂— —CO₂H 1576

H₂C═CH— —CO₂H 1577

H₂C═CHCH₂— —CO₂H 1578

—CH₂F —CO₂H 1579

—CH₂C₆H₅ —CO₂H 1580

—CH₂C₆H₄-p-OCH₃ —CO₂H 1581

—CH₂C₆H₄-p-CH₃ —CO₂H 1582

—CH₂C₆H₄-p-F —CO₂H 1583

—CH₂CH₂C₆H₅ —CO₂H 1584

—CH₂-cyclo-C₆H₁₁ —CO₂H 1585

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1586

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1587

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1588

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1589

—CH₂-cyclo-C₅H₉ —CO₂H 1590

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 1591

—CH₂-2-naphthyl —CO₂H 1592

—H —PO₃H₂ 1593

—CH₃ —PO₃H₂ 1594

—CH₂CH₃ —PO₃H₂ 1595

—CH₂CH₂CH₃ —PO₃H₂ 1596

—CH₂CH₂CH₂CH₃ —PO₃H₂ 1597

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1598

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1599

—CH(CH₃)₂ —PO₃H₂ 1600

—CH₂CH(CH₃)₂ —PO₃H₂ 1601

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1602

-cyclo-C₃H₅ —PO₃H₂ 1603

-cyclo-C₄H₇ —PO₃H₂ 1604

-cyclo-C₅H₉ —PO₃H₂ 1605

-cyclo-C₆H₁₁ —PO₃H₂ 1606

-cyclo-C₇H₁₃ —PO₃H₂ 1607

-cyclo-C₈H₁₅ —PO₃H₂ 1608

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 1609

—CH(CH₂CH₃)₂ —PO₃H₂ 1610

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1611

—C(CH₃)₃ —PO₃H₂ 1612

HC≡CCH₂— —PO₃H₂ 1613

H₂C═CH— —PO₃H₂ 1614

H₂C═CHCH₂— —PO₃H₂ 1615

—CH₂F —PO₃H₂ 1616

—CH₂C₆H₅ —PO₃H₂ 1617

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1618

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 1619

—CH₂C₆H₄-p-F —PO₃H₂ 1620

—CH₂CH₂C₆H₅ —PO₃H₂ 1621

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1622

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1623

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1624

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1625

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1626

—CH₂-cyclo-C₅H₉ —PO₃H₂ 1627

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1628

—CH₂-2-naphthyl —PO₃H₂ 1629

—H -5-Tet 1630

—CH₃ -5-Tet 1631

—CH₂CH₃ -5-Tet 1632

—CH₂CH₂CH₃ -5-Tet 1633

—CH₂CH₂CH₂CH₃ -5-Tet 1634

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 1635

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1636

—CH(CH₃)₂ -5-Tet 1637

—CH₂CH(CH₃)₂ -5-Tet 1638

—CH₂CH₂CH(CH₃)₂ -5-Tet 1639

-cyclo-C₃H₅ -5-Tet 1640

-cyclo-C₄H₇ -5-Tet 1641

-cyclo-C₅H₉ -5-Tet 1642

-cyclo-C₆H₁₁ -5-Tet 1643

-cyclo-C₇H₁₃ -5-Tet 1644

-cyclo-C₈H₁₅ -5-Tet 1645

—CH(CH₃)(CH₂CH₃) -5-Tet 1646

—CH(CH₂CH₃)₂ -5-Tet 1647

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1648

—C(CH₃)₃ -5-Tet 1649

HC≡CCH₂— -5-Tet 1650

H₂C═CH— -5-Tet 1651

H₂C═CHCH₂— -5-Tet 1652

—CH₂F -5-Tet 1653

—CH₂C₆H₅ -5-Tet 1654

—CH₂C₆H₄-p-OCH₃ -5-Tet 1655

—CH₂C₆H₄-p-CH₃ -5-Tet 1656

—CH₂C₆H₄-p-F -5-Tet 1657

—CH₂CH₂C₆H₅ -5-Tet 1658

—CH₂-cyclo-C₆H₁₁ -5-Tet 1659

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1660

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1661

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1662

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1663

—CH₂-cyclo-C₅H₉ -5-Tet 1664

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 1665

—CH₂-2-naphthyl -5-Tet 1666

—H —CO₂H 1667

—CH₃ —CONHOH 1668

—CH₂CH₃ —CO₂H 1669

—CH₂CH₂CH₃ —CO₂H 1670

—CH₂CH₂CH₂CH₃ —CO₂H 1671

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 1672

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1673

—CH(CH₃)₂ —CO₂H 1674

—CH₂CH(CH₃)₂ —CONHOH 1675

—CH₂CH₂CH(CH₃)₂ —CO₂H 1676

-cyclo-C₃H₅ —CO₂H 1677

-cyclo-C₄H₇ —CO₂H 1678

-cyclo-C₅H₉ —CO₂H 1679

-cyclo-C₆H₁₁ —CONHOH 1680

-cyclo-C₇H₁₃ —CO₂H 1681

-cyclo-C₈H₁₅ —CONHOH 1682

—CH(CH₃)(CH₂CH₃) —CONHOH 1683

—CH(CH₂CH₃)₂ —CO₂H 1684

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1685

—C(CH₃)₃ —CO₂H 1686

HC≡CCH₂— —CO₂H 1687

H₂C═CH— —CO₂H 1688

H₂C═CHCH₂— —CO₂H 1689

—CH₂F —CO₂H 1690

—CH₂C₆H₅ —CONHOH 1691

—CH₂C₆H₄-p-OCH₃ —CO₂H 1692

—CH₂C₆H₄-p-CH₃ —CO₂H 1693

—CH₂C₆H₄-p-F —CO₂H 1694

—CH₂CH₂C₆H₅ —CO₂H 1695

—CH₂-cyclo-C₆H₁₁ —CONHOH 1696

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1697

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1698

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1699

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1700

—CH₂-cyclo-C₅H₉ —CO₂H 1701

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 1702

—CH₂-2-naphthyl —CO₂H 1703

—H —PO₃H₂ 1704

—CH₃ —PO₃H₂ 1705

—CH₂CH₃ —PO₃H₂ 1706

—CH₂CH₂CH₃ —PO₃H₂ 1707

—CH₂CH₂CH₂CH₃ —PO₃H₂ 1708

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1709

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1710

—CH(CH₃)₂ —PO₃H₂ 1711

—CH₂CH(CH₃)₂ —PO₃H₂ 1712

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1713

-cyclo-C₃H₅ —PO₃H₂ 1714

-cyclo-C₄H₇ —PO₃H₂ 1715

-cyclo-C₅H₉ —PO₃H₂ 1716

-cyclo-C₆H₁₁ —PO₃H₂ 1717

-cyclo-C₇H₁₃ —PO₃H₂ 1718

-cyclo-C₈H₁₅ —PO₃H₂ 1719

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 1720

—CH(CH₂CH₃)₂ —PO₃H₂ 1721

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1722

—C(CH₃)₃ —PO₃H₂ 1723

HC≡CCH₂— —PO₃H₂ 1724

H₂C═CH— —PO₃H₂ 1725

H₂C═CHCH₂— —PO₃H₂ 1726

—CH₂F —PO₃H₂ 1727

—CH₂C₆H₅ —PO₃H₂ 1728

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1729

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 1730

—CH₂C₆H₄-p-F —PO₃H₂ 1731

—CH₂CH₂C₆H₅ —PO₃H₂ 1732

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1733

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1734

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1735

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1736

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1737

—CH₂-cyclo-C₅H₉ —PO₃H₂ 1738

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1739

—CH₂-2-naphthyl —PO₃H₂ 1740

—H -5-Tet 1741

—CH₃ -5-Tet 1742

—CH₂CH₃ -5-Tet 1743

—CH₂CH₂CH₃ -5-Tet 1744

—CH₂CH₂CH₂CH₃ -5-Tet 1745

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 1746

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1747

—CH(CH₃)₂ -5-Tet 1748

—CH₂CH(CH₃)₂ -5-Tet 1749

—CH₂CH₂CH(CH₃)₂ -5-Tet 1750

-cyclo-C₃H₅ -5-Tet 1751

-cyclo-C₄H₇ -5-Tet 1752

-cyclo-C₅H₉ -5-Tet 1753

-cyclo-C₆H₁₁ -5-Tet 1754

-cyclo-C₇H₁₃ -5-Tet 1755

-cyclo-C₈H₁₅ -5-Tet 1756

—CH(CH₃)(CH₂CH₃) -5-Tet 1757

—CH(CH₂CH₃)₂ -5-Tet 1758

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1759

—C(CH₃)₃ -5-Tet 1760

HC≡CCH₂— -5-Tet 1761

H₂C═CH— -5-Tet 1762

H₂C═CHCH₂— -5-Tet 1763

—CH₂F -5-Tet 1764

—CH₂C₆H₅ -5-Tet 1765

—CH₂C₆H₄-p-OCH₃ -5-Tet 1766

—CH₂C₆H₄-p-CH₃ -5-Tet 1767

—CH₂C₆H₄-p-F -5-Tet 1768

—CH₂CH₂C₆H₅ -5-Tet 1769

—CH₂-cyclo-C₆H₁₁ -5-Tet 1770

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1771

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1772

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1773

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1774

—CH₂-cyclo-C₅H₉ -5-Tet 1775

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 1776

—CH₂-2-naphthyl -5-Tet 1777

—H —CO₂H 1778

—CH₃ —CO₂H 1779

—CH₂CH₃ —CO₂H 1780

—CH₂CH₂CH₃ —CO₂H 1781

—CH₂CH₂CH₂CH₃ —CO₂H 1782

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 1783

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1784

—CH(CH₃)₂ —CO₂H 1785

—CH₂CH(CH₃)₂ —CO₂H 1786

—CH₂CH₂CH(CH₃)₂ —CO₂H 1787

-cyclo-C₃H₅ —CO₂H 1788

-cyclo-C₄H₇ —CO₂H 1789

-cyclo-C₅H₉ —CO₂H 1790

-cyclo-C₆H₁₁ —CO₂H 1791

-cyclo-C₇H₁₃ —CO₂H 1792

-cyclo-C₈H₁₅ —CO₂H 1793

—CH(CH₃)(CH₂CH₃) —CO₂H 1794

—CH(CH₂CH₃)₂ —CO₂H 1795

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1796

—C(CH₃)₃ —CO₂H 1797

HC≡CCH₂— —CO₂H 1798

H₂C═CH— —CO₂H 1799

H₂C═CHCH₂— —CO₂H 1800

—CH₂F —CO₂H 1801

—CH₂C₆H₅ —CO₂H 1802

—CH₂C₆H₄-p-OCH₃ —CO₂H 1803

—CH₂C₆H₄-p-CH₃ —CO₂H 1804

—CH₂C₆H₄-p-F —CO₂H 1805

—CH₂CH₂C₆H₅ —CO₂H 1806

—CH₂-cyclo-C₆H₁₁ —CO₂H 1807

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1808

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1809

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1810

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1811

—CH₂-cyclo-C₅H₉ —CO₂H 1812

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 1813

—CH₂-2-naphthyl —CO₂H 1814

—H —PO₃H₂ 1815

—CH₃ —PO₃H₂ 1816

—CH₂CH₃ —PO₃H₂ 1817

—CH₂CH₂CH₃ —PO₃H₂ 1818

—CH₂CH₂CH₂CH₃ —PO₃H₂ 1819

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1820

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1821

—CH(CH₃)₂ —PO₃H₂ 1822

—CH₂CH(CH₃)₂ —PO₃H₂ 1823

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1824

-cyclo-C₃H₅ —PO₃H₂ 1825

-cyclo-C₄H₇ —PO₃H₂ 1826

-cyclo-C₅H₉ —PO₃H₂ 1827

-cyclo-C₆H₁₁ —PO₃H₂ 1828

-cyclo-C₇H₁₃ —PO₃H₂ 1829

-cyclo-C₈H₁₅ —PO₃H₂ 1830

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 1831

—CH(CH₂CH₃)₂ —PO₃H₂ 1832

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1833

—C(CH₃)₃ —PO₃H₂ 1834

HC≡CCH₂— —PO₃H₂ 1835

H₂C═CH— —PO₃H₂ 1836

H₂C═CHCH₂— —PO₃H₂ 1837

—CH₂F —PO₃H₂ 1838

—CH₂C₆H₅ —PO₃H₂ 1839

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1840

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 1841

—CH₂C₆H₄-p-F —PO₃H₂ 1842

—CH₂CH₂C₆H₅ —PO₃H₂ 1843

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1844

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1845

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1846

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1847

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1848

—CH₂-cyclo-C₅H₉ —PO₃H₂ 1849

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1850

—CH₂-2-naphthyl —PO₃H₂ 1851

—H -5-Tet 1852

—CH₃ -5-Tet 1853

—CH₂CH₃ -5-Tet 1854

—CH₂CH₂CH₃ -5-Tet 1855

—CH₂CH₂CH₂CH₃ -5-Tet 1856

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 1857

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1858

—CH(CH₃)₂ -5-Tet 1859

—CH₂CH(CH₃)₂ -5-Tet 1860

—CH₂CH₂CH(CH₃)₂ -5-Tet 1861

-cyclo-C₃H₅ -5-Tet 1862

-cyclo-C₄H₇ -5-Tet 1863

-cyclo-C₅H₉ -5-Tet 1864

-cyclo-C₆H₁₁ -5-Tet 1865

-cyclo-C₇H₁₃ -5-Tet 1866

-cyclo-C₈H₁₅ -5-Tet 1867

—CH(CH₃)(CH₂CH₃) -5-Tet 1868

—CH(CH₂CH₃)₂ -5-Tet 1869

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1870

—C(CH₃)₃ -5-Tet 1871

HC≡CCH₂— -5-Tet 1872

H₂C═CH— -5-Tet 1873

H₂C═CHCH₂— -5-Tet 1874

—CH₂F -5-Tet 1875

—CH₂C₆H₅ -5-Tet 1876

—CH₂C₆H₄-p-OCH₃ -5-Tet 1877

—CH₂C₆H₄-p-CH₃ -5-Tet 1878

—CH₂C₆H₄-p-F -5-Tet 1879

—CH₂CH₂C₆H₅ -5-Tet 1880

—CH₂-cyclo-C₆H₁₁ -5-Tet 1881

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1882

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1883

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1884

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1885

—CH₂-cyclo-C₅H₉ -5-Tet 1886

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 1887

—CH₂-2-naphthyl -5-Tet 1888

—H —CO₂H 1889

—CH₃ —CO₂H 1890

—CH₂CH₃ —CO₂H 1891

—CH₂CH₂CH₃ —CO₂H 1892

—CH₂CH₂CH₂CH₃ —CO₂H 1893

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 1894

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 1895

—CH(CH₃)₂ —CO₂H 1896

—CH₂CH(CH₃)₂ —CO₂H 1897

—CH₂CH₂CH(CH₃)₂ —CO₂H 1898

-cyclo-C₃H₅ —CO₂H 1899

-cyclo-C₄H₇ —CO₂H 1900

-cyclo-C₅H₉ —CO₂H 1901

-cyclo-C₆H₁₁ —CO₂H 1902

-cyclo-C₇H₁₃ —CO₂H 1903

-cyclo-C₈H₁₅ —CO₂H 1904

—CH(CH₃)(CH₂CH₃) —CO₂H 1905

—CH(CH₂CH₃)₂ —CO₂H 1906

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 1907

—C(CH₃)₃ —CO₂H 1908

HC≡CCH₂— —CO₂H 1909

H₂C═CH— —CO₂H 1910

H₂C═CHCH₂— —CO₂H 1911

—CH₂F —CO₂H 1912

—CH₂C₆H₅ —CO₂H 1913

—CH₂C₆H₄-p-OCH₃ —CO₂H 1914

—CH₂C₆H₄-p-CH₃ —CO₂H 1915

—CH₂C₆H₄-p-F —CO₂H 1916

—CH₂CH₂C₆H₅ —CO₂H 1917

—CH₂-cyclo-C₆H₁₁ —CO₂H 1918

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 1919

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 1920

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 1921

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 1922

—CH₂-cyclo-C₅H₉ —CO₂H 1923

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 1924

—CH₂-2-naphthyl —CO₂H 1925

—H —PO₃H₂ 1926

—CH₃ —PO₃H₂ 1927

—CH₂CH₃ —PO₃H₂ 1928

—CH₂CH₂CH₃ —PO₃H₂ 1929

—CH₂CH₂CH₂CH₃ —PO₃H₂ 1930

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1931

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 1932

—CH(CH₃)₂ —PO₃H₂ 1933

—CH₂CH(CH₃)₂ —PO₃H₂ 1934

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 1935

-cyclo-C₃H₅ —PO₃H₂ 1936

-cyclo-C₄H₇ —PO₃H₂ 1937

-cyclo-C₅H₉ —PO₃H₂ 1938

-cyclo-C₆H₁₁ —PO₃H₂ 1939

-cyclo-C₇H₁₃ —PO₃H₂ 1940

-cyclo-C₈H₁₅ —PO₃H₂ 1941

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 1942

—CH(CH₂CH₃)₂ —PO₃H₂ 1943

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 1944

—C(CH₃)₃ —PO₃H₂ 1945

HC≡CCH₂— —PO₃H₂ 1946

H₂C═CH— —PO₃H₂ 1947

H₂C═CHCH₂— —PO₃H₂ 1948

—CH₂F —PO₃H₂ 1949

—CH₂C₆H₅ —PO₃H₂ 1950

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 1951

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 1952

—CH₂C₆H₄-p-F —PO₃H₂ 1953

—CH₂CH₂C₆H₅ —PO₃H₂ 1954

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1955

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 1956

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 1957

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 1958

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 1959

—CH₂-cyclo-C₅H₉ —PO₃H₂ 1960

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 1961

—CH₂-2-naphthyl —PO₃H₂ 1962

—H -5-Tet 1963

—CH₃ -5-Tet 1964

—CH₂CH₃ -5-Tet 1965

—CH₂CH₂CH₃ -5-Tet 1966

—CH₂CH₂CH₂CH₃ -5-Tet 1967

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 1968

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 1969

—CH(CH₃)₂ -5-Tet 1970

—CH₂CH(CH₃)₂ -5-Tet 1971

—CH₂CH₂CH(CH₃)₂ -5-Tet 1972

-cyclo-C₃H₅ -5-Tet 1973

-cyclo-C₄H₇ -5-Tet 1974

-cyclo-C₅H₉ -5-Tet 1975

-cyclo-C₆H₁₁ -5-Tet 1976

-cyclo-C₇H₁₃ -5-Tet 1977

-cyclo-C₈H₁₅ -5-Tet 1978

—CH(CH₃)(CH₂CH₃) -5-Tet 1979

—CH(CH₂CH₃)₂ -5-Tet 1980

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 1981

—C(CH₃)₃ -5-Tet 1982

HC≡CCH₂— -5-Tet 1983

H₂C═CH— -5-Tet 1984

H₂C═CHCH₂— -5-Tet 1985

—CH₂F -5-Tet 1986

—CH₂C₆H₅ -5-Tet 1987

—CH₂C₆H₄-p-OCH₃ -5-Tet 1988

—CH₂C₆H₄-p-CH₃ -5-Tet 1989

—CH₂C₆H₄-p-F -5-Tet 1990

—CH₂CH₂C₆H₅ -5-Tet 1991

—CH₂-cyclo-C₆H₁₁ -5-Tet 1992

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 1993

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 1994

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 1995

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 1996

—CH₂-cyclo-C₅H₉ -5-Tet 1997

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 1998

—CH₂-2-naphthyl -5-Tet 1999

—H —CO₂H 2000

—CH₃ —CO₂H 2001

—CH₂CH₃ —CO₂H 2002

—CH₂CH₂CH₃ —CO₂H 2003

—CH₂CH₂CH₂CH₃ —CO₂H 2004

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 2005

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2006

—CH(CH₃)₂ —CO₂H 2007

—CH₂CH(CH₃)₂ —CO₂H 2008

—CH₂CH₂CH(CH₃)₂ —CO₂H 2009

—cyclo-C₃H₅ —CO₂H 2010

-cyclo-C₄H₇ —CO₂H 2011

-cyclo-C₅H₉ —CO₂H 2012

-cyclo-C₆H₁₁ —CO₂H 2013

-cyclo-C₇H₁₃ —CO₂H 2014

-cyclo-C₈H₁₅ —CO₂H 2015

—CH(CH₃)(CH₂CH₃) —CO₂H 2016

—CH(CH₂CH₃)₂ —CO₂H 2017

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 2018

—C(CH₃)₃ —CO₂H 2019

HC≡CCH₂— —CO₂H 2020

H₂C═CH— —CO₂H 2021

H₂C═CHCH₂— —CO₂H 2022

—CH₂F —CO₂H 2023

—CH₂C₆H₅ —CO₂H 2024

—CH₂C₆H₄-p-OCH₃ —CO₂H 2025

—CH₂C₆H₄-p-CH₃ —CO₂H 2026

—CH₂C₆H₄-p-F —CO₂H 2027

—CH₂CH₂C₆H₅ —CO₂H 2028

—CH₂-cyclo-C₆H₁₁ —CO₂H 2029

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 2030

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 2031

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 2032

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 2033

—CH₂-cyclo-C₅H₉ —CO₂H 2034

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 2035

—CH₂-2-naphthyl —CO₂H 2036

—H —PO₃H₂ 2037

—CH₃ —PO₃H₂ 2038

—CH₂CH₃ —PO₃H₂ 2039

—CH₂CH₂CH₃ —PO₃H₂ 2040

—CH₂CH₂CH₂CH₃ —PO₃H₂ 2041

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2042

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2043

—CH(CH₃)₂ —PO₃H₂ 2044

—CH₂CH(CH₃)₂ —PO₃H₂ 2045

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 2046

-cyclo-C₃H₅ —PO₃H₂ 2047

-cyclo-C₄H₇ —PO₃H₂ 2048

-cyclo-C₅H₉ —PO₃H₂ 2049

-cyclo-C₆H₁₁ —PO₃H₂ 2050

-cyclo-C₇H₁₃ —PO₃H₂ 2051

-cyclo-C₈H₁₅ —PO₃H₂ 2052

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 2053

—CH(CH₂CH₃)₂ —PO₃H₂ 2054

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 2055

—C(CH₃)₃ —PO₃H₂ 2056

HC≡CCH₂— —PO₃H₂ 2057

H₂C═CH— —PO₃H₂ 2058

H₂C═CHCH₂— —PO₃H₂ 2059

—CH₂F —PO₃H₂ 2060

—CH₂C₆H₅ —PO₃H₂ 2061

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 2062

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 2063

—CH₂C₆H₄-p-F —PO₃H₂ 2064

—CH₂CH₂C₆H₅ —PO₃H₂ 2065

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2066

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 2067

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 2068

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 2069

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2070

—CH₂-cyclo-C₅H₉ —PO₃H₂ 2071

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 2072

—CH₂-2-naphthyl —PO₃H₂ 2073

—H -5-Tet 2074

—CH₃ -5-Tet 2075

—CH₂CH₃ -5-Tet 2076

—CH₂CH₂CH₃ -5-Tet 2077

—CH₂CH₂CH₂CH₃ -5-Tet 2078

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 2079

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 2080

—CH(CH₃)₂ -5-Tet 2081

—CH₂CH(CH₃)₂ -5-Tet 2082

—CH₂CH₂CH(CH₃)₂ -5-Tet 2083

-cyclo-C₃H₅ -5-Tet 2084

-cyclo-C₄H₇ -5-Tet 2085

-cyclo-C₅H₉ -5-Tet 2086

-cyclo-C₆H₁₁ -5-Tet 2087

-cyclo-C₇H₁₃ -5-Tet 2088

-cyclo-C₈H₁₅ -5-Tet 2089

—CH(CH₃)(CH₂CH₃) -5-Tet 2090

—CH(CH₂CH₃)₂ -5-Tet 2091

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 2092

—C(CH₃)₃ -5-Tet 2093

HC≡CCH₂— -5-Tet 2094

H₂C═CH— -5-Tet 2095

H₂C═CHCH₂— -5-Tet 2096

—CH₂F -5-Tet 2097

—CH₂C₆H₅ -5-Tet 2098

—CH₂C₆H₄-p-OCH₃ -5-Tet 2099

—CH₂C₆H₄-p-CH₃ -5-Tet 2100

—CH₂C₆H₄-p-F -5-Tet 2101

—CH₂CH₂C₆H₅ -5-Tet 2102

—CH₂-cyclo-C₆H₁₁ -5-Tet 2103

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 2104

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 2105

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 2106

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 2107

—CH₂-cyclo-C₅H₉ -5-Tet 2108

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 2109

—CH₂-2-naphthyl -5-Tet 2110

—H —CO₂H 2111

—CH₃ —CO₂H 2112

—CH₂CH₃ —CO₂H 2113

—CH₂CH₂CH₃ —CO₂H 2114

—CH₂CH₂CH₂CH₃ —CO₂H 2115

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 2116

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2117

—CH(CH₃)₂ —CO₂H 2118

—CH₂CH(CH₃)₂ —CO₂H 2119

—CH₂CH₂CH(CH₃)₂ —CO₂H 2120

—cyclo-C₃H₅ —CO₂H 2121

-cyclo-C₄H₇ —CO₂H 2122

-cyclo-C₅H₉ —CO₂H 2123

-cyclo-C₆H₁₁ —CO₂H 2124

-cyclo-C₇H₁₃ —CO₂H 2125

-cyclo-C₈H₁₅ —CO₂H 2126

—CH(CH₃)(CH₂CH₃) —CO₂H 2127

—CH(CH₂CH₃)₂ —CO₂H 2128

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 2129

—C(CH₃)₃ —CO₂H 2130

HC≡CCH₂— —CO₂H 2131

H₂C═CH— —CO₂H 2132

H₂C═CHCH₂— —CO₂H 2133

—CH₂F —CO₂H 2134

—CH₂C₆H₅ —CO₂H 2135

—CH₂C₆H₄-p-OCH₃ —CO₂H 2136

—CH₂C₆H₄-p-CH₃ —CO₂H 2137

—CH₂C₆H₄-p-F —CO₂H 2138

—CH₂CH₂C₆H₅ —CO₂H 2139

—CH₂-cyclo-C₆H₁₁ —CO₂H 2140

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 2141

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 2142

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 2143

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 2144

—CH₂-cyclo-C₅H₉ —CO₂H 2145

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 2146

—CH₂-2-naphthyl —CO₂H 2147

—H —PO₃H₂ 2148

—CH₃ —PO₃H₂ 2149

—CH₂CH₃ —PO₃H₂ 2150

—CH₂CH₂CH₃ —PO₃H₂ 2151

—CH₂CH₂CH₂CH₃ —PO₃H₂ 2152

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2153

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2154

—CH(CH₃)₂ —PO₃H₂ 2155

—CH₂CH(CH₃)₂ —PO₃H₂ 2156

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 2157

-cyclo-C₃H₅ —PO₃H₂ 2158

-cyclo-C₄H₇ —PO₃H₂ 2159

-cyclo-C₅H₉ —PO₃H₂ 2160

-cyclo-C₆H₁₁ —PO₃H₂ 2161

-cyclo-C₇H₁₃ —PO₃H₂ 2162

-cyclo-C₈H₁₅ —PO₃H₂ 2163

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 2164

—CH(CH₂CH₃)₂ —PO₃H₂ 2165

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 2166

—C(CH₃)₃ —PO₃H₂ 2167

HC≡CCH₂— —PO₃H₂ 2168

H₂C═CH— —PO₃H₂ 2169

H₂C═CHCH₂— —PO₃H₂ 2170

—CH₂F —PO₃H₂ 2171

—CH₂C₆H₅ —PO₃H₂ 2172

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 2173

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 2174

—CH₂C₆H₄-p-F —PO₃H₂ 2175

—CH₂CH₂C₆H₅ —PO₃H₂ 2176

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2177

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 2178

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 2179

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 2180

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2181

—CH₂-cyclo-C₅H₉ —PO₃H₂ 2182

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 2183

—CH₂-2-naphthyl —PO₃H₂ 2184

—H -5-Tet 2185

—CH₃ -5-Tet 2186

—CH₂CH₃ -5-Tet 2187

—CH₂CH₂CH₃ -5-Tet 2188

—CH₂CH₂CH₂CH₃ -5-Tet 2189

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 2190

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 2191

—CH(CH₃)₂ -5-Tet 2192

—CH₂CH(CH₃)₂ -5-Tet 2193

—CH₂CH₂CH(CH₃)₂ -5-Tet 2194

-cyclo-C₃H₅ -5-Tet 2195

-cyclo-C₄H₇ -5-Tet 2196

-cyclo-C₅H₉ -5-Tet 2197

-cyclo-C₆H₁₁ -5-Tet 2198

-cyclo-C₇H₁₃ -5-Tet 2199

-cyclo-C₈H₁₅ -5-Tet 2200

—CH(CH₃)(CH₂CH₃) -5-Tet 2201

—CH(CH₂CH₃)₂ -5-Tet 2202

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 2203

—C(CH₃)₃ -5-Tet 2204

HC≡ CCH_(2—) -5-Tet 2205

H₂C═CH— -5-Tet 2206

H₂C═CHCH₂— -5-Tet 2207

—CH₂F -5-Tet 2208

—CH₂C₆H₅ -5-Tet 2209

—CH₂C₆H₄-p-OCH₃ -5-Tet 2210

—CH₂C₆H₄-p-CH₃ -5-Tet 2211

—CH₂C₆H₄-p-F -5-Tet 2212

—CH₂CH₂C₆H₅ -5-Tet 2213

—CH₂-cyclo-C₆H₁₁ -5-Tet 2214

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 2215

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 2216

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 2217

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 2218

—CH₂-cyclo-C₅H₉ -5-Tet 2219

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 2220

—CH₂-2-naphthyl -5-Tet 2221

—H —CO₂H 2222

—CH₃ —CO₂H 2223

—CH₂CH₃ —CO₂H 2224

—CH₂CH₂CH₃ —CO₂H 2225

—CH₂CH₂CH₂CH₃ —CO₂H 2226

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 2227

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2228

—CH(CH₃)₂ —CO₂H 2229

—CH₂CH(CH₃)₂ —CO₂H 2230

—CH₂CH₂CH(CH₃)₂ —CO₂H 2231

—cyclo-C₃H₅ —CO₂H 2232

-cyclo-C₄H₇ —CO₂H 2233

-cyclo-C₅H₉ —CO₂H 2234

-cyclo-C₆H₁₁ —CO₂H 2235

-cyclo-C₇H₁₃ —CO₂H 2236

-cyclo-C₈H₁₅ —CO₂H 2237

—CH(CH₃)(CH₂CH₃) —CO₂H 2238

—CH(CH₂CH₃)₂ —CO₂H 2239

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 2240

—C(CH₃)₃ —CO₂H 2241

HC≡CCH₂— —CO₂H 2242

H₂C═CH— —CO₂H 2243

H₂C═CHCH₂— —CO₂H 2244

—CH₂F —CO₂H 2245

—CH₂C₆H₅ —CO₂H 2246

—CH₂C₆H₄-p-OCH₃ —CO₂H 2247

—CH₂C₆H₄-p-CH₃ —CO₂H 2248

—CH₂C₆H₄-p-F —CO₂H 2249

—CH₂CH₂C₆H₅ —CO₂H 2250

—CH₂-cyclo-C₆H₁₁ —CO₂H 2251

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 2252

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 2253

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 2254

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 2255

—CH₂-cyclo-C₅H₉ —CO₂H 2256

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 2257

—CH₂-2-naphthyl —CO₂H 2258

—H —PO₃H₂ 2259

—CH₃ —PO₃H₂ 2260

—CH₂CH₃ —PO₃H₂ 2261

—CH₂CH₂CH₃ —PO₃H₂ 2262

—CH₂CH₂CH₂CH₃ —PO₃H₂ 2263

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2264

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2265

—CH(CH₃)₂ —PO₃H₂ 2266

—CH₂CH(CH₃)₂ —PO₃H₂ 2267

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 2268

-cyclo-C₃H₅ —PO₃H₂ 2269

-cyclo-C₄H₇ —PO₃H₂ 2270

-cyclo-C₅H₉ —PO₃H₂ 2271

-cyclo-C₆H₁₁ —PO₃H₂ 2272

-cyclo-C₇H₁₃ —PO₃H₂ 2273

-cyclo-C₈H₁₅ —PO₃H₂ 2274

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 2275

—CH(CH₂CH₃)₂ —PO₃H₂ 2276

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 2277

—C(CH₃)₃ —PO₃H₂ 2278

HC≡CCH₂— —PO₃H₂ 2279

H₂C═CH— —PO₃H₂ 2280

H₂C═CHCH₂— —PO₃H₂ 2281

—CH₂F —PO₃H₂ 2282

—CH₂C₆H₅ —PO₃H₂ 2283

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 2284

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 2285

—CH₂C₆H₄-p-F —PO₃H₂ 2286

—CH₂CH₂C₆H₅ —PO₃H₂ 2287

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2288

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 2289

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 2290

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 2291

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2292

—CH₂-cyclo-C₅H₉ —PO₃H₂ 2293

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 2294

—CH₂-2-naphthyl —PO₃H₂ 2295

—H -5-Tet 2296

—CH₃ -5-Tet 2297

—CH₂CH₃ -5-Tet 2298

—CH₂CH₂CH₃ -5-Tet 2299

—CH₂CH₂CH₂CH₃ -5-Tet 2300

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 2301

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 2302

—CH(CH₃)₂ -5-Tet 2303

—CH₂CH(CH₃)₂ -5-Tet 2304

—CH₂CH₂CH(CH₃)₂ -5-Tet 2305

-cyclo-C₃H₅ -5-Tet 2306

-cyclo-C₄H₇ -5-Tet 2307

-cyclo-C₅H₉ -5-Tet 2308

-cyclo-C₆H₁₁ -5-Tet 2309

-cyclo-C₇H₁₃ -5-Tet 2310

-cyclo-C₈H₁₅ -5-Tet 2311

—CH(CH₃)(CH₂CH₃) -5-Tet 2312

—CH(CH₂CH₃)₂ -5-Tet 2313

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 2314

—C(CH₃)₃ -5-Tet 2315

HC≡ CCH₂— -5-Tet 2316

H₂C═CH— -5-Tet 2317

H₂C═CHCH₂— -5-Tet 2318

—CH₂F -5-Tet 2319

—CH₂C₆H₅ -5-Tet 2320

—CH₂C₆H₄-p-OCH₃ -5-Tet 2321

—CH₂C₆H₄-p-CH₃ -5-Tet 2322

—CH₂C₆H₄-p-F -5-Tet 2323

—CH₂CH₂C₆H₅ -5-Tet 2324

—CH₂-cyclo-C₆H₁₁ -5-Tet 2325

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 2326

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 2327

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 2328

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 2329

—CH₂-cyclo-C₅H₉ -5-Tet 2330

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 2331

—CH₂-2-naphthyl -5-Tet 2332

—H —CO₂H 2333

—CH₃ —CO₂H 2334

—CH₂CH₃ —CO₂H 2335

—CH₂CH₂CH₃ —CO₂H 2336

—CH₂CH₂CH₂CH₃ —CO₂H 2337

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 2338

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2339

—CH(CH₃)₂ —CO₂H 2340

—CH₂CH(CH₃)₂ —CO₂H 2341

—CH₂CH₂CH(CH₃)₂ —CO₂H 2342

—cyclo-C₃H₅ —CO₂H 2343

-cyclo-C₄H₇ —CO₂H 2344

-cyclo-C₅H₉ —CO₂H 2345

-cyclo-C₆H₁₁ —CO₂H 2346

-cyclo-C₇H₁₃ —CO₂H 2347

-cyclo-C₈H₁₅ —CO₂H 2348

—CH(CH₃)(CH₂CH₃) —CO₂H 2349

—CH(CH₂CH₃)₂ —CO₂H 2350

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 2351

—C(CH₃)₃ —CO₂H 2352

HC≡CCH₂— —CO₂H 2353

H₂C═CH— —CO₂H 2354

H₂C═CHCH₂— —CO₂H 2355

—CH₂F —CO₂H 2356

—CH₂C₆H₅ —CO₂H 2357

—CH₂C₆H₄-p-OCH₃ —CO₂H 2358

—CH₂C₆H₄-p-CH₃ —CO₂H 2359

—CH₂C₆H₄-p-F —CO₂H 2360

—CH₂CH₂C₆H₅ —CO₂H 2361

—CH₂-cyclo-C₆H₁₁ —CO₂H 2362

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 2363

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 2364

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 2365

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 2366

—CH₂-cyclo-C₅H₉ —CO₂H 2367

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 2368

—CH₂-2-naphthyl —CO₂H 2369

—H —PO₃H₂ 2370

—CH₃ —PO₃H₂ 2371

—CH₂CH₃ —PO₃H₂ 2372

—CH₂CH₂CH₃ —PO₃H₂ 2373

—CH₂CH₂CH₂CH₃ —PO₃H₂ 2374

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2375

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2376

—CH(CH₃)₂ —PO₃H₂ 2377

—CH₂CH(CH₃)₂ —PO₃H₂ 2378

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 2379

-cyclo-C₃H₅ —PO₃H₂ 2380

-cyclo-C₄H₇ —PO₃H₂ 2381

-cyclo-C₅H₉ —PO₃H₂ 2382

-cyclo-C₆H₁₁ —PO₃H₂ 2383

-cyclo-C₇H₁₃ —PO₃H₂ 2384

-cyclo-C₈H₁₅ —PO₃H₂ 2385

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 2386

—CH(CH₂CH₃)₂ —PO₃H₂ 2387

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 2388

—C(CH₃)₃ —PO₃H₂ 2389

HC≡CCH₂— —PO₃H₂ 2390

H₂C═CH— —PO₃H₂ 2391

H₂C═CHCH₂— —PO₃H₂ 2392

—CH₂F —PO₃H₂ 2393

—CH₂C₆H₅ —PO₃H₂ 2394

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 2395

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 2396

—CH₂C₆H₄-p-F —PO₃H₂ 2397

—CH₂CH₂C₆H₅ —PO₃H₂ 2398

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2399

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 2400

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 2401

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 2402

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2403

—CH₂-cyclo-C₅H₉ —PO₃H₂ 2404

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 2405

—CH₂-2-naphthyl —PO₃H₂ 2406

—H -5-Tet 2407

—CH₃ -5-Tet 2408

—CH₂CH₃ -5-Tet 2409

—CH₂CH₂CH₃ -5-Tet 2410

—CH₂CH₂CH₂CH₃ -5-Tet 2411

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 2412

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 2413

—CH(CH₃)₂ -5-Tet 2414

—CH₂CH(CH₃)₂ -5-Tet 2415

—CH₂CH₂CH(CH₃)₂ -5-Tet 2416

-cyclo-C₃H₅ -5-Tet 2417

-cyclo-C₄H₇ -5-Tet 2418

-cyclo-C₅H₉ -5-Tet 2419

-cyclo-C₆H₁₁ -5-Tet 2420

-cyclo-C₇H₁₃ -5-Tet 2421

-cyclo-C₈H₁₅ -5-Tet 2422

—CH(CH₃)(CH₂CH₃) -5-Tet 2423

—CH(CH₂CH₃)₂ -5-Tet 2424

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 2425

—C(CH₃)₃ -5-Tet 2426

HC≡ CCH₂— -5-Tet 2427

H₂C═CH— -5-Tet 2428

H₂C═CHCH₂— -5-Tet 2429

—CH₂F -5-Tet 2430

—CH₂C₆H₅ -5-Tet 2431

—CH₂C₆H₄-p-OCH₃ -5-Tet 2432

—CH₂C₆H₄-p-CH₃ -5-Tet 2433

—CH₂C₆H₄-p-F -5-Tet 2434

—CH₂CH₂C₆H₅ -5-Tet 2435

—CH₂-cyclo-C₆H₁₁ -5-Tet 2436

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 2437

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 2438

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 2439

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 2440

—CH₂-cyclo-C₅H₉ -5-Tet 2441

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 2442

—CH₂-2-naphthyl -5-Tet 2443

—H —CO₂H 2444

—CH₃ —CO₂H 2445

—CH₂CH₃ —CO₂H 2446

—CH₂CH₂CH₃ —CO₂H 2447

—CH₂CH₂CH₂CH₃ —CO₂H 2448

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 2449

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2450

—CH(CH₃)₂ —CO₂H 2451

—CH₂CH(CH₃)₂ —CO₂H 2452

—CH₂CH₂CH(CH₃)₂ —CO₂H 2453

—cyclo-C₃H₅ —CO₂H 2454

-cyclo-C₄H₇ —CO₂H 2455

-cyclo-C₅H₉ —CO₂H 2456

-cyclo-C₆H₁₁ —CO₂H 2457

-cyclo-C₇H₁₃ —CO₂H 2458

-cyclo-C₈H₁₅ —CO₂H 2459

—CH(CH₃)(CH₂CH₃) —CO₂H 2460

—CH(CH₂CH₃)₂ —CO₂H 2461

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 2462

—C(CH₃)₃ —CO₂H 2463

HC≡CCH₂— —CO₂H 2464

H₂C═CH— —CO₂H 2465

H₂C═CHCH₂— —CO₂H 2466

—CH₂F —CO₂H 2467

—CH₂C₆H₅ —CO₂H 2468

—CH₂C₆H₄-p-OCH₃ —CO₂H 2469

—CH₂C₆H₄-p-CH₃ —CO₂H 2470

—CH₂C₆H₄-p-F —CO₂H 2471

—CH₂CH₂C₆H₅ —CO₂H 2472

—CH₂-cyclo-C₆H₁₁ —CONHOH 2473

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 2474

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 2475

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 2476

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 2477

—CH₂-cyclo-C₅H₉ —CO₂H 2478

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 2479

—CH₂-2-naphthyl —CO₂H 2480

—H —PO₃H₂ 2481

—CH₃ —PO₃H₂ 2482

—CH₂CH₃ —PO₃H₂ 2483

—CH₂CH₂CH₃ —PO₃H₂ 2484

—CH₂CH₂CH₂CH₃ —PO₃H₂ 2485

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2486

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2487

—CH(CH₃)₂ —PO₃H₂ 2488

—CH₂CH(CH₃)₂ —PO₃H₂ 2489

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 2490

-cyclo-C₃H₅ —PO₃H₂ 2491

-cyclo-C₄H₇ —PO₃H₂ 2492

-cyclo-C₅H₉ —PO₃H₂ 2493

-cyclo-C₆H₁₁ —PO₃H₂ 2494

-cyclo-C₇H₁₃ —PO₃H₂ 2495

-cyclo-C₈H₁₅ —PO₃H₂ 2496

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 2497

—CH(CH₂CH₃)₂ —PO₃H₂ 2498

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 2499

—C(CH₃)₃ —PO₃H₂ 2500

HC≡CCH₂— —PO₃H₂ 2501

H₂C═CH— —PO₃H₂ 2502

H₂C═CHCH₂— —PO₃H₂ 2503

—CH₂F —PO₃H₂ 2504

—CH₂C₆H₅ —PO₃H₂ 2505

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 2506

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 2507

—CH₂C₆H₄-p-F —PO₃H₂ 2508

—CH₂CH₂C₆H₅ —PO₃H₂ 2509

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2510

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 2511

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 2512

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 2513

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2514

—CH₂-cyclo-C₅H₉ —PO₃H₂ 2515

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 2516

—CH₂-2-naphthyl —PO₃H₂ 2517

—H -5-Tet 2518

—CH₃ -5-Tet 2519

—CH₂CH₃ -5-Tet 2520

—CH₂CH₂CH₃ -5-Tet 2521

—CH₂CH₂CH₂CH₃ -5-Tet 2522

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 2523

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 2524

—CH(CH₃)₂ -5-Tet 2525

—CH₂CH(CH₃)₂ -5-Tet 2526

—CH₂CH₂CH(CH₃)₂ -5-Tet 2527

-cyclo-C₃H₅ -5-Tet 2528

-cyclo-C₄H₇ -5-Tet 2529

-cyclo-C₅H₉ -5-Tet 2530

-cyclo-C₆H₁₁ -5-Tet 2531

-cyclo-C₇H₁₃ -5-Tet 2532

-cyclo-C₈H₁₅ -5-Tet 2533

—CH(CH₃)(CH₂CH₃) -5-Tet 2534

—CH(CH₂CH₃)₂ -5-Tet 2535

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 2536

—C(CH₃)₃ -5-Tet 2537

HC≡CCH₂— -5-Tet 2538

H₂C═CH— -5-Tet 2539

H₂C═CHCH₂— -5-Tet 2540

—CH₂F -5-Tet 2541

—CH₂C₆H₅ -5-Tet 2542

—CH₂C₆H₄-p-OCH₃ -5-Tet 2543

—CH₂C₆H₄-p-CH₃ -5-Tet 2544

—CH₂C₆H₄-p-F -5-Tet 2545

—CH₂CH₂C₆H₅ -5-Tet 2546

—CH₂-cyclo-C₆H₁₁ -5-Tet 2547

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 2548

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 2549

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 2550

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 2551

—CH₂-cyclo-C₅H₉ -5-Tet 2552

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 2553

—CH₂-2-naphthyl -5-Tet 2554

—H —CO₂H 2555

—CH₃ —CO₂H 2556

—CH₂CH₃ —CO₂H 2557

—CH₂CH₂CH₃ —CO₂H 2558

—CH₂CH₂CH₂CH₃ —CO₂H 2559

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 2560

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2561

—CH(CH₃)₂ —CO₂H 2562

—CH₂CH(CH₃)₂ —CO₂H 2563

—CH₂CH₂CH(CH₃)₂ —CO₂H 2564

-cyclo-C₃H₅ —CO₂H 2565

-cyclo-C₄H₇ —CO₂H 2566

-cyclo-C₅H₉ —CO₂H 2567

-cyclo-C₆H₁₁ —CO₂H 2568

-cyclo-C₇H₁₃ —CO₂H 2569

-cyclo-C₈H₁₅ —CO₂H 2570

—CH(CH₃)(CH₂CH₃) —CO₂H 2571

—CH(CH₂CH₃)₂ —CO₂H 2572

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 2573

—C(CH₃)₃ —CO₂H 2574

HC≡CCH₂— —CO₂H 2575

H₂C═CH— —CO₂H 2576

H₂C═CHCH₂— —CO₂H 2577

—CH₂F —CO₂H 2578

—CH₂C₆H₅ —CO₂H 2579

—CH₂C₆H₄-p-OCH₃ —CO₂H 2580

—CH₂C₆H₄-p-CH₃ —CO₂H 2581

—CH₂C₆H₄-p-F —CO₂H 2582

—CH₂CH₂C₆H₅ —CO₂H 2583

—CH₂-cyclo-C₆H₁₁ —CO₂H 2584

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 2585

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 2586

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 2587

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 2588

—CH₂-cyclo-C₅H₉ —CO₂H 2589

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 2590

—CH₂-2-naphthyl —CO₂H 2591

—H —PO₃H₂ 2592

—CH₃ —PO₃H₂ 2593

—CH₂CH₃ —PO₃H₂ 2594

—CH₂CH₂CH₃ —PO₃H₂ 2595

—CH₂CH₂CH₂CH₃ —PO₃H₂ 2596

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2597

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2598

—CH(CH₃)₂ —PO₃H₂ 2599

—CH₂CH(CH₃)₂ —PO₃H₂ 2600

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 2601

-cyclo-C₃H₅ —PO₃H₂ 2602

-cyclo-C₄H₇ —PO₃H₂ 2603

-cyclo-C₅H₉ —PO₃H₂ 2604

-cyclo-C₆H₁₁ —PO₃H₂ 2605

-cyclo-C₇H₁₃ —PO₃H₂ 2606

-cyclo-C₈H₁₅ —PO₃H₂ 2607

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 2608

—CH(CH₂CH₃)₂ —PO₃H₂ 2609

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 2610

—C(CH₃)₃ —PO₃H₂ 2611

HC≡CCH₂— —PO₃H₂ 2612

H₂C═CH— —PO₃H₂ 2613

H₂C═CHCH₂— —PO₃H₂ 2614

—CH₂F —PO₃H₂ 2615

—CH₂C₆H₅ —PO₃H₂ 2616

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 2617

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 2618

—CH₂C₆H₄-p-F —PO₃H₂ 2619

—CH₂CH₂C₆H₅ —PO₃H₂ 2620

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2621

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 2622

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 2623

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 2624

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2625

—CH₂-cyclo-C₅H₉ —PO₃H₂ 2626

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 2627

—CH₂-2-naphthyl —PO₃H₂ 2628

—H -5-Tet 2629

—CH₃ -5-Tet 2630

—CH₂CH₃ -5-Tet 2631

—CH₂CH₂CH₃ -5-Tet 2632

—CH₂CH₂CH₂CH₃ -5-Tet 2633

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 2634

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 2635

—CH(CH₃)₂ -5-Tet 2636

—CH₂CH(CH₃)₂ -5-Tet 2637

—CH₂CH₂CH(CH₃)₂ -5-Tet 2638

-cyclo-C₃H₅ -5-Tet 2639

-cyclo-C₄H₇ -5-Tet 2640

-cyclo-C₅H₉ -5-Tet 2641

-cyclo-C₆H₁₁ -5-Tet 2642

-cyclo-C₇H₁₃ -5-Tet 2643

-cyclo-C₈H₁₅ -5-Tet 2644

—CH(CH₃)(CH₂CH₃) -5-Tet 2645

—CH(CH₂CH₃)₂ -5-Tet 2646

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 2647

—C(CH₃)₃ -5-Tet 2648

HC≡CCH₂— -5-Tet 2649

H₂C═CH— -5-Tet 2650

H₂C═CHCH₂— -5-Tet 2651

—CH₂F -5-Tet 2652

—CH₂C₆H₅ -5-Tet 2653

—CH₂C₆H₄-p-OCH₃ -5-Tet 2654

—CH₂C₆H₄-p-CH₃ -5-Tet 2655

—CH₂C₆H₄-p-F -5-Tet 2656

—CH₂CH₂C₆H₅ -5-Tet 2657

—CH₂-cyclo-C₆H₁₁ -5-Tet 2658

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 2659

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 2660

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 2661

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 2662

—CH₂-cyclo-C₅H₉ -5-Tet 2663

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 2664

—CH₂-2-naphthyl -5-Tet 2665

—H —CO₂H 2666

—CH₃ —CO₂H 2667

—CH₂CH₃ —CO₂H 2668

—CH₂CH₂CH₃ —CO₂H 2669

—CH₂CH₂CH₂CH₃ —CO₂H 2670

—CH₂CH₂CH₂CH₂CH₃ —CO₂H 2671

—CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2672

—CH(CH₃)₂ —CO₂H 2673

—CH₂CH(CH₃)₂ —CO₂H 2674

—CH₂CH₂CH(CH₃)₂ —CO₂H 2675

-cyclo-C₃H₅ —CO₂H 2676

-cyclo-C₄H₇ —CO₂H 2677

-cyclo-C₅H₉ —CO₂H 2678

-cyclo-C₆H₁₁ —CO₂H 2679

-cyclo-C₇H₁₃ —CO₂H 2680

-cyclo-C₈H₁₅ —CO₂H 2681

—CH(CH₃)(CH₂CH₃) —CO₂H 2682

—CH(CH₂CH₃)₂ —CO₂H 2683

—CH(CH₃)(CH₂CH₂CH₃) —CO₂H 2684

—C(CH₃)₃ —CO₂H 2685

HC≡CCH₂— —CO₂H 2686

H₂C═CH— —CO₂H 2687

H₂C═CHCH₂— —CO₂H 2688

—CH₂F —CO₂H 2689

—CH₂C₆H₅ —CO₂H 2690

—CH₂C₆H₄-p-OCH₃ —CO₂H 2691

—CH₂C₆H₄-p-CH₃ —CO₂H 2692

—CH₂C₆H₄-p-F —CO₂H 2693

—CH₂CH₂C₆H₅ —CO₂H 2694

—CH₂-cyclo-C₆H₁₁ —CO₂H 2695

—CH₂-cyclo-C₆H₁₀-4-F —CO₂H 2696

—CH₂-cyclo-C₆H₁₀-4-CH₃ —CO₂H 2697

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —CO₂H 2698

—CH₂CH₂-cyclo-C₆H₁₁ —CO₂H 2699

—CH₂-cyclo-C₅H₉ —CO₂H 2700

—CH₂CH₂-cyclo-C₅H₉ —CO₂H 2701

—CH₂-2-naphthyl —CO₂H 2702

—H —PO₃H₂ 2703

—CH₃ —PO₃H₂ 2704

—CH₂CH₃ —PO₃H₂ 2705

—CH₂CH₂CH₃ —PO₃H₂ 2706

—CH₂CH₂CH₂CH₃ —PO₃H₂ 2707

—CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2708

—CH₂CH₂CH₂CH₂CH₂CH₃ —PO₃H₂ 2709

—CH(CH₃)₂ —PO₃H₂ 2710

—CH₂CH(CH₃)₂ —PO₃H₂ 2711

—CH₂CH₂CH(CH₃)₂ —PO₃H₂ 2712

-cyclo-C₃H₅ —PO₃H₂ 2713

-cyclo-C₄H₇ —PO₃H₂ 2714

-cyclo-C₅H₉ —PO₃H₂ 2715

-cyclo-C₆H₁₁ —PO₃H₂ 2716

-cyclo-C₇H₁₃ —PO₃H₂ 2717

-cyclo-C₈H₁₅ —PO₃H₂ 2718

—CH(CH₃)(CH₂CH₃) —PO₃H₂ 2719

—CH(CH₂CH₃)₂ —PO₃H₂ 2720

—CH(CH₃)(CH₂CH₂CH₃) —PO₃H₂ 2721

—C(CH₃)₃ —PO₃H₂ 2722

HC≡CCH₂— —PO₃H₂ 2723

H₂C═CH— —PO₃H₂ 2724

H₂C═CHCH₂— —PO₃H₂ 2725

—CH₂F —PO₃H₂ 2726

—CH₂C₆H₅ —PO₃H₂ 2727

—CH₂C₆H₄-p-OCH₃ —PO₃H₂ 2728

—CH₂C₆H₄-p-CH₃ —PO₃H₂ 2729

—CH₂C₆H₄-p-F —PO₃H₂ 2730

—CH₂CH₂C₆H₅ —PO₃H₂ 2731

—CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2732

—CH₂-cyclo-C₆H₁₀-4-F —PO₃H₂ 2733

—CH₂-cyclo-C₆H₁₀-4-CH₃ —PO₃H₂ 2734

—CH₂-cyclo-C₆H₁₀-4-OCH₃ —PO₃H₂ 2735

—CH₂CH₂-cyclo-C₆H₁₁ —PO₃H₂ 2736

—CH₂-cyclo-C₅H₉ —PO₃H₂ 2737

—CH₂CH₂-cyclo-C₅H₉ —PO₃H₂ 2738

—CH₂-2-naphthyl —PO₃H₂ 2739

—H -5-Tet 2740

—CH₃ -5-Tet 2741

—CH₂CH₃ -5-Tet 2742

—CH₂CH₂CH₃ -5-Tet 2743

—CH₂CH₂CH₂CH₃ -5-Tet 2744

—CH₂CH₂CH₂CH₂CH₃ -5-Tet 2745

—CH₂CH₂CH₂CH₂CH₂CH₃ -5-Tet 2746

—CH(CH₃)₂ -5-Tet 2747

—CH₂CH(CH₃)₂ -5-Tet 2748

—CH₂CH₂CH(CH₃)₂ -5-Tet 2749

-cyclo-C₃H₅ -5-Tet 2750

-cyclo-C₄H₇ -5-Tet 2751

-cyclo-C₅H₉ -5-Tet 2752

-cyclo-C₆H₁₁ -5-Tet 2753

-cyclo-C₇H₁₃ -5-Tet 2754

-cyclo-C₈H₁₅ -5-Tet 2755

—CH(CH₃)(CH₂CH₃) -5-Tet 2756

—CH(CH₂CH₃)₂ -5-Tet 2757

—CH(CH₃)(CH₂CH₂CH₃) -5-Tet 2758

—C(CH₃)₃ -5-Tet 2759

HC≡CCH₂— -5-Tet 2760

H₂C═CH— -5-Tet 2761

H₂C═CHCH₂— -5-Tet 2762

—CH₂F -5-Tet 2763

—CH₂C₆H₅ -5-Tet 2764

—CH₂C₆H₄-p-OCH₃ -5-Tet 2765

—CH₂C₆H₄-p-CH₃ -5-Tet 2766

—CH₂C₆H₄-p-F -5-Tet 2767

—CH₂CH₂C₆H₅ -5-Tet 2768

—CH₂-cyclo-C₆H₁₁ -5-Tet 2769

—CH₂-cyclo-C₆H₁₀-4-F -5-Tet 2770

—CH₂-cyclo-C₆H₁₀-4-CH₃ -5-Tet 2771

—CH₂-cyclo-C₆H₁₀-4-OCH₃ -5-Tet 2772

—CH₂CH₂-cyclo-C₆H₁₁ -5-Tet 2773

—CH₂-cyclo-C₅H₉ -5-Tet 2774

—CH₂CH₂-cyclo-C₅H₉ -5-Tet 2775

—CH₂-2-naphthyl -5-Tet 2776 H₂N(CH₂)₉— —H —CO₂H 2777 H₂N(CH₂)₉— —CH₃ —CO₂H 2778 H₂N(CH₂)₉— —CH₂CH₃ —CO₂H 2779 H₂N(CH₂)₉— —CH₂CH₂CH₃ —CO₂H 2780 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₃ —CO₂H 2781 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₂CH₃ —CO₂H 2782 H₂N(CH₂)₉— —CH₂CH₂CH₂CH₂CH₂CH₃ —CO₂H 2783 H₂N(CH₂)₉— —CH(CH₃)₂ —CO₂H 2784 H₂N(CH₂)₉— —CH₂CH(CH₃)₂ —CO₂H 2785 H₂N(CH₂)₉— —CH₂CH₂CH(CH₃)₂ —CO₂H 2786 H₂N(CH₂)₉— -cyclo-C₃H₅ —CO₂H

BIOLOGICAL EVALUATION Assay A: NMT Enzyme Inhibition Assays

Recombinant Candida albicans and human NMTs were expressed and purified from E. coli using previously described protocols. [D. A. Towler et al, Proc. Natl. Acad. Sci. USA, 84, 2707-2712 (1987); R. C. Weigand et al, J. Biol. Chem., 267, 8591-8598 (1992); R. J. Duronio et al, Proc. Natl. Acad. Sci. USA, 89, 4129-4133 (1992)] The ability of compounds to inhibit Candida NMT enzymatic activity was assessed using a radiochemical HPLC end-point assay as described previously for Saccharomyces cerevisiae and human NMTs. [D. Towler et al, Proc. Natl. Acad. Sci. USA, 83, 2812-2816 (1986); W. J. Rocque et al, J. Biol. Chem., 268, 9964-9971 (1991)] The donor substrate [³H]myristoyl-coenzyme A was enzymatically synthesized from [³H]myristic acid (50 Ci/mmol, Amersham, Arlington Heights, Ill.) and coenzyme A (Fluka Chemical Corp., Ronkonkoma, N.Y.), and purified as described previously. [W. J. Rocque et al, J. Biol. Chem., 268, 9964-9971 (1991)] The peptide acceptor substrate GNAASARR-NH₂ was prepared by solid-phase peptide synthesis using the t-Boc amino acid methodology, followed by HF treatment and reverse-phase HPLC purification. Inhibitor stock solutions were prepared at 22 mM in DMSO; the final concentration of DMSO in each assay was 0.5% (v/v). Inhibition assays were carried out by combining variable amounts of inhibitor or buffer with 0.11 mmoles of [³H]myristoyl-coenzyme A (1 μCi, 9.09 Ci/mmol) and 2.2 nmoles of GNAASARR-NH₂ in a total volume of 60 μL of 0.2 M N-[2-hydroxy-ethyl]piperazine-N′-[2-ethanesulfonic acid], pH 7.4, 2 mM DL-dithiothreitol, 0.2 mM ethylene glycol-bis-(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid, and initiating the reaction by the addition of 50 μL of a Candida NMT solution (7-12 ng/50 μL). Assays with human NMT were identical except that they used 60-75 ng/50 μL of enzyme solution and 0.22 nmoles of GNAASARR-NH₂. The reaction was quenched after 10 minutes at 24° C. by the addition of ice-cold MeOH, and the reaction products were separated and measured using C4 reverse-phase HPLC (Vydac 214TP₁₀₄₁₅; Separations Group, Hesperia, Calif.) and in-line scintillation counting using a Radiomatic A250 (Packard Instruments, Downers Grove, Ill.) and Ecolite(+) (ICN Biomedical, Costa Mesa, Calif.) as the scintillant. Selectivity was determined by calculating the ratio of the IC₅₀ against human NMT to the IC₅₀ against C. albicans NMT.

Organism-culture and Source:

Antifungal Screens were set up initially against Candida albicans, strain B311, and Cryotococcus neoformans, strain L210425. Both pathogens, (originally from the stock culture collection, Medical mycology research center, Washington university-Barnes hospital), were obtained from Dr.Kobayashi, Prof.of infectious diseases, Washington University, St.Louis, Mo.

All cultures are maintained at 30° C. on Sabouraud's dextrose agar slants and subcultured at monthly intervals to fresh medium. All inocula for susceptibility testing are prepared in yeast nitogen base(YNB, Difco) broth.

A loopful of growth from Sabouraud dextrose agar slant is inoculated into 4 ml of YNB broth media and incubated at 30° C. overnight (18-24 hrs) with constant agitation (Gyratory Shaker, New Brunswick Scientific). Prior to setting up susceptibility testing, the organisms are counted in a hemocytometer, and diluted as needed into assay media.

Antifungal Susceptibility Testing:

1) (Assay at DH 5.4/30° C. Incubation/YNB Media).

Antifungal assays were carried out initially by a modification of the method published by Jones, et. al; (1), and communicated to Searle by Dr. Kobayashi, Washington University. [R. N. Jones et al, Manual of Clinical Microbiology, 4th ed., (1985)]

The antifungal susceptibility testing consists of a microdilution broth procedure performed in 96 well microtiter plates (Costar, cat#3799). Briefly, test compounds from a 20 mM stock solution in DMSO are diluted into sterile, deionized water (final DMSO concentration not exceeding 1%), to yield 2× the desired concentration (100 uM, 10 uM and 1 uM for an initial screen, or a selected concentration range in serial 2 fold dilutions for EC₅₀ determination). One hundred microliters (100 ul) of each concentration is dispensed into triplicate wells of a 96 well microtiter plate. Appropriate dilutions of a suspension of C.albicans (1×10⁶ cells/ml) in 2× YNB is distributed into each of the wells, including growth control wells containing no test compound as well as control wells with 0.5% DMSO. Amphotericin B at 0.05, 1 and 5 ug/ml is included in each assay plate as a positive control. The plates are incubated at 30° C. and cell growth is scored by reading the absorbance at 590 nm on an Elisa plate reader(Dynatech, MR.5000). EC₅₀, the concentration of compound inhibiting growth by 50% compared to untreated controls, is calculated for 24 hrs and 48 hrs.

To determine MFC (minimal fungicidal concentration), all wells that have no visible growth are subcultured on to Sabouraud dextrose agar. These subcultures are incubated at 30° C. and examined for growth at daily intervals upto four days. The MFC is defined as the lowest concentration of compound showing<than 10 cfu on subculture. Parallel, identical assays are set up simultaneously to test compound effect on Crytococcus neoformans.

2) Assay at pH 7.0/35° C. Incubation/(Candida Strains Only).

Based on several papers published during 1990-1993 regarding the standardization of testing procedures at multiple research centers, and the finding that, inoculum size, pH of media, and the temperature of incubation drastically affect the antifungal activity of several compounds, particularly in the Azole class of antifungals, an additional assay was configured at pH 7.0 for Candida albicans. [M. A. Pfaller et al, Antimicrobial Agents and Chemotherapy, 34, 1648-1654 (1990); F. C. Odds et al, Antimicrobial Agents and Chemotherapy, 36, 1727-1737 (1992); R. A. Cook et al, Antimicrobial Agents and Chemotherapy, 34, 1542-1545 (1990)]

The assay format is identical to the first one with the following modifications: C.albicans cells are diluted to 1×10³ cells/ml into 2× buffered YNB (YNB buffered with 1.65 mM MOPS, pH 7.0, with the addition of 2% Dextrose and 0.08% casamino acids mixture, bio 101. inc,cat #10420-100). Incubation is carried out at 35° C. instead of 30° C., and cell growth is monitored at 590 nm at 24 and 48 hrs as described. All other aspects of the assay are identical. This assay was validated with amphotericin B, fluconazole, cilofungin (Ly-121019), Nikkomycin and terbinafine using the following Candida strains- (C.albicans, B311, C.parasilosis, C.tropicalis, C.lusitaniae, C.glabrata, and C. albicans 516)-Table II. All strains were from Dr. Kobayashi, Washington university. Antifungal activity is expressed as EC₅₀-(μM) at 24 hr and 48 hr for both sets of assay conditions for Candida albicans, and pH 5.4 assay only for Cryrtococcus neoformans.

TABLE II: ANTIFUNGAL ACTIVITY OF KNOWN COMPOUNDS AGAINST CANDIDA STRAINS-(pH 7.0/35° C. / 1X 10³ CELLS/mL)/ EC₅₀ - 48 HRS C.albicans Compound (b311) (516) C.para C.trop. C.lusi. C.glab. Amphotericin 0.11 0.14 0.31 0.44 0.42 0.47 (μg/mL) Fluconazole 0.71 0.65 0.91 2.6 0.6 26 (μg/mL) Terbinafine 4.4 3.2 0.2 >100 0.4 >100 (μM) Ly 12109 0.6 0.6 32 0.6 6.6 6.1 (μM) Nikkomycin 4.5 11 13 >100 28 >100 (μM)

TABLE III: ANTIFUNGAL ACTIVITY OF NMT INHIBITORS pH 5.4 ASSAY COMPOUND C.neoformans pH 7.0 ASSAY EX. # C.albicans EC₅₀ -μM C. albicans 1 24h 33 >100 >100 48h 77 >100 >100 2 24h 35 >100 >100 48h 70 >100 >100 3 24h 33 >100 >100 48h 58 >100 >100 4 24h 63 >100 >100    48h >100 >100 >100 5 24h 68 >100 >100 48h 81 >100 >100 6 24h 80 >100 >100    48h >100 >100 >100 7 24h 97 >100 >100    48h >100 >100 >100 9    24h >100 >100 >100    48h >100 >100 >100 10    24h >100 >100 >100    48h >100 >100 >100 Comp. A    24h >400 >100 >100    48h >400 >100 >100

TABLE IV: ACTIVITY (EC₅₀) OF EXAMPLE #2 and COMPARATOR COMPOUND A AGAINST DIFFERENT STRAINS OF CANDIDA (pH 5.4 assay) / 24 hr) Strain C.alb C.alb Compound (B311) C.para. C.trop. C.lusi. C.glab. (516) Ex. #2 35 40 >250 >250 >250 >250 Compar. >400 >250 >250 >250 >250 >250 Comp. A

TABLE V Biological Activity of Example #1-11 Compounds IC₅₀ IC₅₀ caEC₅₀ Ex. caNMT hNMT 24 hours No. (μM) (μM) Selectivity (μM) 1 0.4 850 2200 33 2 1.4 810 560 35 3 80% NT ND 33 @ 11 μM 4 6.7 NT ND 63 5 27% NT ND 68 @ 10 μM 6 36% NT ND 80 @ 10 μM 7 100 NT ND 97 8 78% NT ND >100 @ 10 μM 9 6 NT ND >100 10 40% NT ND >100 @ 10 μM 11 18 NT ND >100 caNMT = Candida albicans NMT; hNMT = human NMT; IC₅₀ reported or % inhibition at ˜10 μM. ca = Candida albicans NT = Not tested; ND = not determined.

Assay B: Gel Shift Assay for Assessing the Degree of N-myristoylation of Arf1p in Strains Containing Wild Type or Mutant NMTs

Rationale

N-myristoylation of C. albicans ADP ribosylation factor (Arf), produces a change in its electrophoretic mobility during SDS-polyacrylamide gel electrophoresis. The acylated species migrates more rapidly than the nonmyristoylated species [J. K. Lodge et al, J. Biol. Chem., 269, 2996-3009 (1994)].

Recent genetic studies have shown that NMT is essential for vegetative growth of Candida albicans [R. A Weinberg et al, Mol. Micro., in press, (1995)]. This conclusion was based on the following set of observations. A strain of C. albicans was constructed in which one copy of NMT was partially deleted and disrupted. A Gly⁴⁴⁷→Asp mutation was introduced into the second MMT allele. This mutation produces marked reductions in catalytic efficiency at 24 and 37° C., as judged by in vitro kinetic studies of the purified wild type and mutant enzymes. The growth characteristics of isogenic VMT/IMT, NMT/Δnmt, and nmtΔ/nmtG447D C. albicans strains were subsequently assessed under a variety of conditions. Only the nmtΔ/nmtG447D strain requires myristate for growth on YPD medium at 24 or 37° C. When nmtΔ/nmtG447D cells are switched from YPD supplemented with 500 μM myristate to YPD that does not contain any supplemental myristate, 60% of the cells die within 4 h (assay=the ability to form colonies on YPD/500 μM myristate). Protein gel shift assays of Arf N-myristoylation indicated that when exponentially growing nmtΔ/nmtG447D cells were incubated at 24° C. in the presence of myristate, 100% of Arf is N-myristoylated. After 4 h of incubation in the absence of myristate, nonmyristoyalted Arf represents ˜40-50% of total cellular Arf.

Based on these findings, acylation of C. albicans Arf, measured using this protein gel shift assay, was used to define the effects of peptide analog inhibitors of C. albicans NMT on the efficiency of protein N-myristoylation in cultures of this fungal pathogen.

The assay was performed as follows. A single colony of Candida albicans strain MONCA105 NMT, [R. A Weinberg et al, Mol. Micro., in press, (1995)] was innoculated into YPD medium (YPD=1% yeast extract, 2% peptone, 2% dextrose). Cultures were shaken at 24° C. for 12-16 h. Cells were recovered by centrifugation, washed 3 times with sterile PBS, pH 7.4 and resuspended in YPD at an OD₆₀₀ of 1.0-1.5. Fifty microliters of a 20 mM stock solution of peptide analog (prepared in sterile deionized H₂O) were added to a sterile polypropylene tube containing 4.5 mL of fresh YPD medium. Five hundred microliters of the C. albicans culture was then added to the tubes. Controls consisted of no added peptide analog (i.e. water alone).The tubes were incubated at 24° C. with vigorous shaking for 2 hr or 4 hr. For each experiment, duplicate tubes were assayed for each condition and at each time point. Cells were recovered by centrifugation, resuspended in 200 μL of Lysis Buffer (0.125M Tris-HCl, pH 6.8/4% SDS), and transferred to microfuge tubes containing 200 μL of glass beads (bead diameter=425-600 μm, Sigma).The slurry was vortexed 3 times for 1 min each. Between each cycle of vortexing, the tubes were placed on ice for 1 min. The mixture was then placed in a boiling water bath for 10 min, vortexed once again for 1 min and subsequently spun at 10,000×g for 2 min. The cleared supernatant fraction was removed, spun again at 10,000×g for 5 min and the total protein concentration determined. Equal masses of protein from each sample (100 μg) were reduced, denatured, fractionated by electrophoresis through a 12% polyacrylamide gel containing 0.1% SDS [U. K. Laemmli, Nature, 227, 680-685 (1970)] and transferred to PVDF membranes (Millipore). The resulting Western blots were probed with rabbit antiserum R23 which was raised against a peptide (SNSLKNST) encompassing the C-terminal 8 residues of S. cerevisiae Arf1p (kindly supplied by Richard Kahn, Lab of Biological Chemistry, NCI, NIH; final dilution=1:4000 in I-Block buffer from Tropix). Antigen-antibody complexes were visualized using the Western-Light Immunoblotting System (Tropix). The secondary antibody was an alkaline phosphatase-conjugated goat-anti-Rabbit IgG. 200 μM Example #2 produces ˜10% reduction in Arf N-myristoylation within 2 h. The optical isomer (Comparator Compound A) is not an inhibitor of purified C. albicans Nmt in vitro. 200 μM of this compound produces no detectable reduction of Arf acylation in vivo at either the 2 h or the 4 h time point.

Also embraced within this invention is a class of pharmaceutical compositions comprising one or more compounds of Formula I in association with one or more non-toxic, pharmaceutically acceptable carriers and/or diluents and/or adjuvants (collectively referred to herein as “carrier” materials) and, if desired, other active ingredients. The compounds of the present. invention may be administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in a dose effective.for the treatment intended. Therapeutically effective doses of the compounds of the present invention required to prevent or arrest the progress of the medical condition are readily ascertained by one of ordinary skill in the art. The compounds and compositions may, for example, be administered intravascularly, intraperitoneally, subcutaneously, intramuscularly or topically.

For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, capsule, suspension or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient. Examples of such dosage units are tablets or capsules. These may with advantage contain an amount of active ingredient from about 1 to 500 mg, preferably from about 10 to 250 mg. A suitable daily dose may vary widely depending on the condition of the patient and other factors. However, a dose of from about 0.01 to about 15 mg/kg body weight, particularly from about 0.1 to 10 mg/kg body weight, may be appropriate.

The active ingredient may also be administered by injection as a composition wherein, for example, saline, dextrose or water may be used as a suitable carrier. A suitable daily dose may range from about 0.01 to 15 mg/kg body weight injected per day in multiple doses depending on the disease being treated. A preferred daily dose would be from about 0.5 to about 10 mg/kg body weight. Compounds indicated for prophylactic therapy will preferably be administered in a daily dose generally in a range from about 0.01 mg to about 15 mg per kilogram of body weight per day. A more preferred dosage will be a range from about 0.1 mg to about 10 mg per kilogram of body weight. Most preferred is a dosage in a range from about 0.5 to about 5 mg per kilogram of body weight per day.

A suitable dose can be administered, in multiple sub-doses per day. These sub-doses may be administered in unit dosage forms. Typically, a dose or sub-dose may contain from about 1 mg to about 500 mg of active compound per unit dosage form. A more preferred dosage will contain from about 10 mg to about 250 mg of active compound per unit dosage form. Most preferred is a dosage form containing from about 20 mg to about 150 mg of active compound per unit dose.

The dosage regimen for treating a disease condition with the compounds and/or compositions of this invention is selected in accordance with a variety of factors, including the type, age, weight, sex and medical condition of the patient, the severity of the disease, the route of administration, and the particular compound employed, and thus may vary widely.

For therapeutic purposes, the compounds of this invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient administration. Such capsules or tablets may contain a controlled-release formulation as may be provided in a dispersion of active compound in hydroxypropylmethyl cellulose. Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulations for oral administration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art.

A preferred method of treatment includes administering a compound of the invention topically to treat primary infections occurring in the vaginal tract. Another preferred method of treatment includes administering a compound of the invention by gastrointestinal absorption, either by oral ingestion or by suppository, to treat a systemic fungal infection.

Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limitations.

5 1 10 PRT Candida albicans 1 Gly Cys Gly Ala Ser Val Pro Val Asp Asp 1 5 10 2 8 PRT Saccharomyces cerevisiae 2 Gly Leu Tyr Ala Ser Lys Leu Ser 1 5 3 8 PRT Saccharomyces cerevisiae 3 Ala Leu Tyr Ala Ser Lys Leu Ser 1 5 4 8 PRT Saccharomyces cerevisiae 4 Gly Asn Ala Ala Ser Ala Arg Arg 1 5 5 8 PRT Saccharomyces cerevisiae 5 Ser Asn Ser Leu Lys Asn Ser Thr 1 5 

What is claimed is:
 1. A method of inhibiting growth of Candida Albicans in a subject afflicted therewith comprising administering to said subject a compound, for a time and under conditions effective to inhibit growth of Candida Albicans, selected from compounds of Formula II:

wherein R¹ is selected from aminoalkyl, aminoalkylcycloalkyl, aminoalkylcycloalkylalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, monoalkylaminocycloalkylalkyl, dialkylaminocycloalkylalkyl, aminoalkylarylalkyl, monoalkylaminoalkylarylalkyl, dialkylaminoalkylarylalkyl,. aminocycloalkyl, monocycloalkylaminoalkyl, monoalkylaminocycloalkyl, monocycloalkylaminocycloalkyl, dialkylaminocycloalkyl, aminocycloalkylarylalkyl, aminoalkylarylcycloalkyl, aminocycloalkylarylcycloalkyl, monocycloalkylaminoalkylarylalkyl, monoalkylaminocycloalkylarylalkyl, monoalkylaminoalkylarylcycloalkyl, monocycloalkylaminocycloalkylarylalkyl, monocycloalkylaminoalkylarylcycloalkyl, monoalkylaminocycloalkylarylcycloalkyl, monocycloalkylaminocycloalkylarylcycloalkyl, dialkylaminocycloalkylarylalkyl, dialkylaminoalkylarylcycloalkyl, dialkylaminocycloalkylarylcycloalkyl, heterocyclic-A-alkyl, heterocyclic-A-alkylarylalkyl, heterocyclic-A-cycloalkyl, heterocyclic-A-cycloalkylarylalkyl, heterocyclic-A-alkylarylcycloalkyl, heterocyclic-A-cycloalkylarylcycloalkyl, heteroaryl-A-alkyl, heteroaryl-A-alkylarylalkyl, heteroaryl-A-cycloalkyl, heteroaryl-A-cycloalkylarylalkyl, hetergaryl-A-alkylarylcycloalkyl and heteroaryl-A-cycloalkylarylcycloalkyl, wherein A is either a covalent bond or is a moiety selected from

wherein R⁰ is selected from hydrido, alkyl, cycloalkyl and cycloalkylalkyl; wherein any foregoing heterocyclic-containing moiety may be fused to an aryl ring to form an arylheterocyclic moiety, and wherein any foregoing heteroaryl-containing moiety may be fused to an aryl ring to form an arylheteroaryl moiety, and wherein any of said heterocyclic moiety, heteroaryl moiety, arylheterocyclic moiety and arylheteroaryl moiety may be independently substituted at one or more substitutable positions with one or more radicals selected from halo, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, amino, aminoacyl, aminocarbonylalkoxy, monoalkylamino, dialkylamino, alkoxy, alkylthio, aralkyl and aryl, with the proviso that said heterocyclic moiety is selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl, and with the further proviso that said heteroaryl moiety is selected from imidazolyl and pyridinyl; wherein R² is a radical selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, bicycloalkyl, alkenyl, cycloalkenyl, fused bicycloalkenyl, cycloalkyl fused to cycloalkenyl, alkenylalkyl, alkynyl, aralkyl and aryl, wherein any of said R² radicals having a substitutable position may be substituted by one or more radicals selected from alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, cycloalkenyl, fused bicycloalkenyl, cycloalkyl fused to cycloalkenyl, alkenylalkyl, alkynyl, halo, haloalkyl, alkoxy, alkoxyalkyl, alkylthio, aralkoxy, aryloxy, arylthio, aralkyl, aryl, alkoxycarbonyl, cycloalkoxycarbonyl, alkoxycarbonylalkyl and cycloalkoxycarbonylcycloalkyl; wherein Y is selected from hydroxyalkyl, hydroxycycloalkyl, hydroxycycloalkylalkyl, hydroxyaryl, hydroxyaminocarbonylaralkyl, hydroxyaminocarbonyl, hydroxyaminocarbonylalkyl, hydroxyaminocarbonylcycloalkyl, hydroxyaminocarbonylcycloalkylalkyl, hydroxyaminocarbonylaryl, carboxyl, carboxyalkyl, carboxycycloalkyl, carboxycyloalkylalkyl, tetrazolyl, tetrazolylalkyl, tetrazolylcycloalkyl, tetrazolylcycloalkylalkyl, phosphinic acid, monoalkylphosphinic acid, dialkylphosphinic acid, monocycloalkylphosphinic acid, dicycloalkylphosphinic acid, monocycloalkylalkylphosphinic acid, dicycloalkylalkylphosphinic acid, mixed monoalkylmonocycloalkylphosphinic acid, mixed monoalkylmonocycloalkylalkylphosphinic acid, mixed monocycloalkylmonocycloalkylalkylphosphinic acid, monoarylphosphinic acid, diarylphosphinic acid, mixed monoalkyl-monoarylphosphinic acid, mixed monocycloalkyl-monoarylphosphinic acid, mixed monocycloalkylalkyl-monoarylphosphinic acid, phosphonic acid, alkylphosphonic acid, cycloalkylphosphonic acid, cycloalkylalkylphosphonic acid, aralkylphosphonic acid and arylphosphonic acid; or an acceptable ester, amide, or salt thereof.
 2. The method of claim 1 wherein R¹ is selected from aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, aminoalkylphenylalkyl, monoalkylaminoalkylphenylalkyl, dialkylaminoalkylphenylalkyl, heterocyclicalkyl, heterocyclicalkylphenylalkyl, heteroarylalkyl, heteroarylalkylphenylalkyl, heterocycliccylcoalkyl, heterocycliccycloalkylalkyl, heteroarylcycloalkyl and heteroarylcycloalkylalkyl wherein any foregoing heterocyclic moiety may be fused to a phenyl ring to form a benzoheterocyclic moiety and wherein any foregoing heteroaryl moiety may be fused to a phenyl ring to form a benzoheteroaryl moiety, and wherein any of said heterocyclic moiety, benzoheterocyclic moiety, heteroaryl moiety and benzoheteroaryl moiety may be substituted at one or more substitutable positions with one or more radicals selected from halo, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkylthio, phenylalkyl and phenyl; with the proviso that said heterocyclic moiety is selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl, and with the further proviso that said heteroaryl is selected from imidazolyl and pyridinyl; wherein R² is a radical selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl, wherein any of said R² radicals having a substitutable position may be substituted by one or more radicals selected from alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, halo, haloalkyl, alkoxy, alkylthio, phenylalkyl, phenyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, alkoxycarbonyl and alkoxycarbonylalkyl; wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

wherein X is selected from alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl; wherein R⁹ is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl; or an acceptable ester, amide, or salt thereof.
 3. The method of claim 2 wherein R¹ is selected from

wherein W is a divalent radical of the general structure

wherein W is selected from alkyl and cycloalkyl; wherein each of R¹⁰ and R¹¹ is independently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl; wherein further R¹⁰ and R¹¹ may be taken together to form a saturated heterocyclic ring system having five or six ring members and having at least one nitrogen atom as a ring member and optionally having a second heteroatom selected from an oxygen, nitrogen or sulfur atom as a ring member, said heterocyclic ring system selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl; wherein each of R¹² and R¹³ is independently selected from hydrido, alkyl and haloalkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, halo, cycloalkyl, alkoxy, alkylthio, phenylalkyl and phenyl; wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, phenylalkyl and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy; wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

 with each of R⁴ through R⁸ independently selected from —CH₂—, —CH₂CH₂— and —CH₂CH₂CH₂—; wherein R⁹ is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl; or an acceptable ester, amide, or salt thereof.
 4. The method of claim 3 wherein R¹ is selected from

wherein each of R¹⁰ and R¹¹ is independently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, phenylalkyl and phenyl; wherein further R¹⁰ and R¹¹ may be taken together to form a saturated heterocyclic ring system having five or six ring members and having at least one nitrogen atom as a ring member and optionally having a second heteroatom selected from an oxygen, nitrogen or sulfur atom as a ring member, said heterocyclic ring system selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl; wherein each of R¹² and R¹³ is independently selected from hydrido, alkyl and haloalkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, halo, cycloalkyl, alkoxy, alkylthio, phenylalkyl and phenyl; wherein each of m, n, p and r is a whole number independently selected from 3 through 15; wherein each of q and t is a whole number independently selected from 1 through 6; wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, phenylalkyl, and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy; wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

 with each of R⁴ through R⁸ independently selected from —CH₂—, —CH₂CH₂— and —CH₂CH₂CH₂; wherein R⁹ is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl and benzyl; or an acceptable ester, amide, or salt thereof.
 5. The method of claim 4 wherein R¹ is selected from

wherein each of R¹⁰ and R¹¹ is independently selected from hydrido and alkyl; wherein further R¹⁰ and R¹¹ may be taken together to form a saturated heterocyclic ring system having five or six ring members and having at least one nitrogen atom as a ring member and optionally having a second hetero atom selected from an oxygen, nitrogen or sulfur atom as a ring member, said heterocyclic ring system selected from morpholino, thiomorpholino, piperazinyl, piperidinyl and pyrrolidinyl; wherein each of R¹² and R¹³ is independently selected from hydrido, alkyl and haloalkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, halo, cycloalkyl, alkoxy, alkylthio, phenylalkyl and phenyl; wherein each of m, n, p and r is a whole number independently selected from 6 through 14; wherein each of q and t is a whole number independently selected from 3 through 6; wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, tetrahydronaphthyl, decahydronaphthyl, naphthylalkyl, tetrahydronaphthylalkyl, decahydronaphthylalkyl, naphthylcycloalkyl, tetrahydronaphthylcycloalkyl, decahydronaphthylalkyl, phenylalkyl, and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy; wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is a divalent radical of the general structure

 with each of R⁴ through R⁸ independently selected from —CH₂—, —CH₂CH₂— and —CH₂CH₂CH₂; wherein R⁹ is selected from hydrido, alkyl and benzyl; or an acceptable ester, amide, or salt thereof.
 6. The method of claim 5 wherein R¹ is selected from

wherein each of R¹⁰ and R¹¹ is independently selected from hydrido and alkyl; wherein each of R¹² and R¹³ is independently selected from hydrido and alkyl; wherein R¹⁴ is selected from hydrido, alkyl, haloalkyl, alkoxy and alkylthio; wherein each of m, n, p and r is a whole number independently selected from 6 through 14; wherein each of q and t is a whole number independently selected from 3 through 6; wherein R² is a moiety selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, haloalkyl, naphthyl, naphthylalkyl, phenylalkyl, and phenyl, wherein any said R² moiety may be substituted at a substitutable position by one or more radicals selected from alkyl, halo and alkoxy; wherein Y is selected from

 wherein each of R⁴ through R⁸ is either a covalent bond or is —CH₂; wherein R⁹ is selected from hydrido, alkyl and benzyl; or an acceptable ester, amide, or salt thereof.
 7. The method of claim 6 wherein R¹ is selected from H₂N(CH₂)₉—, H₂N(CH₂)₁₀—, H₂N(CH₂)₁₁—, CH₃NH(CH₂)₁₀—, (CH₃)₂N(CH₂)₁₀—, p-[H₂N(CH₂)₆]C₆H₄CH₂—, p-[H₂N(CH₂)₈]C₆H₄CH₂—, p-[H₂N(CH₂)₉]C₆H₄CH₂—, p-[H₂N(CH₂)₁₀]C₆H₄CH₂—, p-[H₂N(CH₂)₆]C₆H₄CH(CH₃)—, p-[H₂N(CH₂)₈]C₆H₄CH(CH₃)—, p-[H₂N(CH₂)₉]C₆H₄CH(CH₃)—, p-[H₂N(CH₂)₁₀]C₆H₄CH(CH₃)—,

wherein R² is selected from —H, —CH₃, —CH₂CH₃, -CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH₂CH₂CH₃, —CH₂CH₂CH₂CH₂CH₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂CH₂CH(CH₃)₂, -cyclo-C₃H₅, -cyclo-C₄H₇, -cyclo-C₅H₉, -cyclo-C₆H₁₁, -cyclo-C₇H₁₃, -cyclo-C₈H₁₅, —CH(CH₃)(CH₂CH₃), —CH(CH₂CH₃)₂, —CH(CH₃)(CH₂CH₂CH₃), —C(CH₃)₃, HC≡CCH₂—, H₂C═CH—, H₂C═CHCH₂—, —CH₂F, —CH₂C₆H₅, —CH₂C₆H₄-p-OCH₃, —CH₂C₆H₄-p-CH₃, —CH₂C₆H₄-p-F, —CH₂CH₂C₆H₅, —CH₂-cyclo-C₆H₁₁, —CH₂-cyclo-C₆H₁₀-4-F, —CH₂-cyclo-C₆H₁₀-4-CH₃, —CH₂-cyclo-C₆H₁₀-4-OCH₃, —CH₂CH₂-cyclo-C₆H₁₁, —CH₂-cyclo-C₅H₉, —CH₂CH₂-cyclo-C₅H₉ and —CH₂-2-naphthyl; wherein Y is selected from —CO₂H, —CH₂CO₂H, CONHOH, —PO₃H₂, and

or an acceptable ester, amide, or salt thereof.
 8. The method of claim 7 wherein said compound is selected from compounds and their diastereoisomers of the group consisting of L-Alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]oxopropyl]-L-seryl]-L-lysyl]-, (±), bis-trifluoroacetate; L-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate; L-Alanine, 3-cyclohexyl-N-[[(11-amino-undecanoyl)-L-seryl]-L-lysyl]-, bis-trifluoroacetate; L-Leucine, N-[[(11-amino-undecanoyl)-L-seryl]-L-lysyl]-, bis-trifluoroacetate; L-Alanine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate; L-Alanine, 3-phenyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate; L-iso-Leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate; L-Leucine, N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate; Lysinamide, N-[1-cyclohexyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate; Lysinamide, N-[1-cyclooctyl-2-carboxyethyl]-N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-, ±, bis-trifluoroacetate; and D-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate.
 9. The method of claim 8 wherein said compound is L-Alanine, 3-cyclohexyl-N-[N²-[N-[2-[4-[4-[2-methyl-1H-imidazol-1-yl)butyl]phenyl] oxopropyl]-L-seryl]-L-lysyl]-, (±), bis-trifluoroacetate.
 10. The method of claim 8 wherein said compound is L-Alanine, 3-cyclohexyl-N-[N²-[N-[[4-[4-(2-methyl-1H-imidazol-1-yl)butyl]phenyl]acetyl]-L-seryl]-L-lysyl]-, bis-trifluoroacetate.
 11. The method of claim 1 wherein said compound is administered topically.
 12. The method of claim 1 wherein said compound is administered by gastrointestinal absorption to inhibit systemic growth of Candida Albicans. 